716 results on '"Valenzuela, Carmen"'
Search Results
2. Micro problems with macro consequences: accumulation of persistent organic pollutants and microplastics in human breast milk and in human milk substitutes
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Caba-Flores, Mario Daniel, Martínez-Valenzuela, Carmen, Cárdenas-Tueme, Marcela, and Camacho-Morales, Alberto
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- 2023
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3. NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer’s clinical syndrome: the ATHENEA randomized clinical trial
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Sosa, Saily, Bringas, Giosmany, Urrutia, Nelky, Peñalver, Ana Ivis, López, Danay, González, Evelio, Fernández, Ana, Hernández, Zenaida Milagros, Viña, Ariel, Peña, Yamile, Batista, Juan Felipe, Valenzuela, Carmen, León, Kalet, Crombet, Tania, Rodríguez, Teresita, and Pérez, Leslie
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- 2023
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4. Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function
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Vera-Zambrano, Alba, Baena-Nuevo, Maria, Rinné, Susanne, Villegas-Esguevillas, Marta, Barreira, Bianca, Telli, Gokcen, de Benito-Bueno, Angela, Blázquez, José Antonio, Climent, Belén, Pérez-Vizcaino, Francisco, Valenzuela, Carmen, Decher, Niels, Gonzalez, Teresa, and Cogolludo, Angel
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- 2023
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5. Isolation and characterization of endophytic bacteria from maize and giant reed with biotechnological and biocontrol potential against Rhizoctonia zeae
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Morales-Ruiz, Estefanía, primary, Zamudio-Aguilasocho, Gloria M., additional, Martínez-Valenzuela, Carmen, additional, Maldonado-Mendoza, Ignacio E., additional, and Cordero-Ramírez, Jesús Damián, additional
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- 2022
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6. A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism
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Galán-Vidal, Jesús, Socuéllamos, Paula G., Baena-Nuevo, María, Contreras, Lizbeth, González, Teresa, Pérez-Poyato, María S., Valenzuela, Carmen, González-Lamuño, Domingo, and Gandarillas, Alberto
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- 2022
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7. Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension
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Díaz del Campo, Lucia S., García-Redondo, Ana B., Rodríguez, Cristina, Zaragoza, Carlos, Duro-Sánchez, Santiago, Palmas, Francesco, de Benito-Bueno, Angela, Socuéllamos, Paula G., Peraza, Diego A., Rodrigues-Díez, Raquel, Valenzuela, Carmen, Dalli, Jesmond, Salaices, Mercedes, and Briones, Ana M.
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- 2023
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8. Functional Assembly of Kv7.1/Kv7.5 Channels With Emerging Properties on Vascular Muscle Physiology
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Oliveras, Anna, Roura Ferrer, Meritxell, Solé, Laura, Cruz, Alicia de la, Prieto, Angela, Etxebarria, Ainhoa, Manils, Joan, Morales Cano, Daniel, Condom, Enric, Soler, Concepció, Cogolludo Torralba, Ángel Luis, Valenzuela, Carmen, Villarroel, Alvaro, Comes, Núria, Felipe, Antonio, Oliveras, Anna, Roura Ferrer, Meritxell, Solé, Laura, Cruz, Alicia de la, Prieto, Angela, Etxebarria, Ainhoa, Manils, Joan, Morales Cano, Daniel, Condom, Enric, Soler, Concepció, Cogolludo Torralba, Ángel Luis, Valenzuela, Carmen, Villarroel, Alvaro, Comes, Núria, and Felipe, Antonio
- Abstract
Objective—Voltage-dependent K+ (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fail to modulate smooth muscle reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form functional heterotetrameric channels increasing the channel diversity in vascular smooth muscles. Approach and Results—Kv7.1 and Kv7.5 currents elicited in arterial myocytes, oocyte, and mammalian expression systems suggest the formation of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5 associations were confirmed by coimmunoprecipitation, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching experiments. Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum. Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles demonstrated that the predominant presence of Kv7.5 stimulates release of Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological studies supported that KCNE1 and KCNE3 regulatory subunits further increased the channel diversity. Finally, the analysis of rat isolated myocytes and human blood vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression, which may lead to channel diversity. Conclusions—Kv7.1 and Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. Because the lipid raft localization of ion channels is crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient spatial and temporal regulation of smooth muscle function. Our results shed light on the debate about the contribution of Kv7 channels to vasoconstrictio, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub
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- 2024
9. Interaction of angiotensin II with the angiotensin type 2 receptor inhibits the cardiac transient outward potassium current
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Caballero Collado, Ricardo, Gómez García, Ricardo, Moreno, Fernández, Ignacio, Núñez Fernández, Lucía, González, Teresa, Arias, Cristina, Guizy, Miriam, Valenzuela, Carmen, Tamargo Menéndez, Juan, Delpón Mosquera, María Eva, Caballero Collado, Ricardo, Gómez García, Ricardo, Moreno, Fernández, Ignacio, Núñez Fernández, Lucía, González, Teresa, Arias, Cristina, Guizy, Miriam, Valenzuela, Carmen, Tamargo Menéndez, Juan, and Delpón Mosquera, María Eva
- Abstract
Objective: The Ca2+ -independent transient outward K+ current (Ito) plays a crucial role in shaping the cardiac action potential. In the present study, we examined whether angiotensin II (AngII) regulated the Ito as well as the putative intracellular cascade responsible for the effects. Methods: Ito was recorded in rat ventricular myocytes using the nystatin-perforated patch-clamp configuration. Results: AngII (0.1 microM) inhibited Ito (21.9+/-4.8% at +40 mV), but not the IK1, in a voltage- and time-independent manner. The inhibition decreased at concentrations higher than 1 microM resulting in a bell-shaped dose-response curve (IC50 = 3.1+/-1.5 microM). The blocking effects were abolished in the presence of the type 2 AngII receptor (AT2R) antagonist PD123319, but not in the presence of the selective type 1 AngII receptor (AT1R) antagonist candesartan. Moreover, the selective AT2R agonist CGP42112A completely reproduced the effects of AngII (20.5+/-2.4% of block at +40 mV), indicating that AngII-induced Ito block was mediated via stimulation of AT2R. Furthermore, selective stimulation of AT2R by CGP42112A significantly prolonged the rat atrial action potentials recorded using conventional microelectrode techniques. The AngII-induced inhibition of I(to) was not modified by either Npi-nitro-L-arginine-methyl ester (L-NAME) or eicosatetrayonic acid (ETYA), indicating that neither the nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) system nor the arachidonic acid cascade was implicated in the effects of AngII on Ito. However, the AngII-induced Ito inhibition was completely abolished by the serine/threonine phosphatase type 2A (PP2A) inhibitors, okadaic acid and cantharidin, but not by the inactive analog of okadaic acid, 1-norokadaone. Intracellular application of PP2A decreased Kv4.2 currents recorded in transiently transfected Chinese hamster ovary cells (CHO). Conclusion: These results indicate that AngII activates PP2A through the stimulation of the, Comisión Interministerial de Ciencia y Tecnología, Comunidad de Madrid, Instituto de Salud Carlos III, Pfizer Foundation, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub
- Published
- 2024
10. Encapsulation of Azotobacter vinelandii ATCC 12837 in Alginate-Na Beads as a Tomato Seedling Inoculant
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Conde-Avila, Victoria, Ortega-Martínez, Luis Daniel, Loera, Octavio, Pérez-Armendáriz, Beatriz, and Martínez Valenzuela, Carmen
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- 2022
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11. Growth, respiratory activity and chlorpyrifos biodegradation in cultures of Azotobacter vinelandii ATCC 12837
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Conde-Avila, Victoria, Peña, Carlos, Pérez-Armendáriz, Beatriz, Loera, Octavio, Martínez Valenzuela, Carmen, Leyva Morales, José Belisario, Jesús Bastidas Bastidas, Pedro de, Salgado-Lugo, Holjes, and Ortega Martínez, Luis Daniel
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- 2021
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12. Routing of Kv7.1 to endoplasmic reticulum plasma membrane junctions.
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Serrano‐Novillo, Clara, Estadella, Irene, Navarro‐Pérez, María, Oliveras, Anna, de Benito‐Bueno, Angela, Socuéllamos, Paula G., Bosch, Manel, Coronado, María José, Sastre, Daniel, Valenzuela, Carmen, Soeller, Christian, and Felipe, Antonio
- Subjects
CELL membranes ,ENDOPLASMIC reticulum ,ACTION potentials ,PROTEIN structure ,TRANSMISSION electron microscopy - Abstract
Aim: The voltage‐gated Kv7.1 channel, in association with the regulatory subunit KCNE1, contributes to the IKs current in the heart. However, both proteins travel to the plasma membrane using different routes. While KCNE1 follows a classical Golgi‐mediated anterograde pathway, Kv7.1 is located in endoplasmic reticulum‐plasma membrane junctions (ER‐PMjs), where it associates with KCNE1 before being delivered to the plasma membrane. Methods: To characterize the channel routing to these spots we used a wide repertoire of methodologies, such as protein expression analysis (i.e. protein association and biotin labeling), confocal (i.e. immunocytochemistry, FRET, and FRAP), and dSTORM microscopy, transmission electron microscopy, proteomics, and electrophysiology. Results: We demonstrated that Kv7.1 targeted ER‐PMjs regardless of the origin or architecture of these structures. Kv2.1, a neuronal channel that also contributes to a cardiac action potential, and JPHs, involved in cardiac dyads, increased the number of ER‐PMjs in nonexcitable cells, driving and increasing the level of Kv7.1 at the cell surface. Both ER‐PMj inducers influenced channel function and dynamics, suggesting that different protein structures are formed. Although exhibiting no physical interaction, Kv7.1 resided in more condensed clusters (ring‐shaped) with Kv2.1 than with JPH4. Moreover, we found that VAMPs and AMIGO, which are Kv2.1 ancillary proteins also associated with Kv7.1. Specially, VAP B, showed higher interaction with the channel when ER‐PMjs were stimulated by Kv2.1. Conclusion: Our results indicated that Kv7.1 may bind to different structures of ER‐PMjs that are induced by different mechanisms. This variable architecture can differentially affect the fate of cardiac Kv7.1 channels. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Effect of temperature on growth, survival, thermal behavior, and critical thermal maximum in the juveniles of Macrobrachium occidentale (Holthuis, 1950) (Decapoda: Caridea: Palaemonidae) from Mexico
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Hernández-Sandoval, Pedro, Diaz-Herrera, Fernando, Diaz-Gaxiola, Jesus Manuel, Martinez-Valenzuela, Carmen, and Garcia-Guerrero, Marcelo
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- 2018
14. Differential effect of Androctonus australis hector venom components on macrophage KV channels: electrophysiological characterization
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Khemili, Dalila, Valenzuela, Carmen, Laraba-Djebari, Fatima, and Hammoudi-Triki, Djelila
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- 2019
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15. An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients
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Saavedra, Danay, Añé-Kourí, Ana Laura, Sánchez, Naivy, Filgueira, Lázaro Manuel, Betancourt, Julio, Herrera, Carlos, Manso, Leniel, Chávez, Elibet, Caballero, Armando, Hidalgo, Carlos, Lorenzo, Geydi, Cepeda, Meylan, Valenzuela, Carmen, Ramos, Mayra, León, Kalet, Mazorra, Zaima, and Crombet, Tania
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- 2020
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16. DECOLORACIÓN DE EFLUENTES TEXTILES QUE CONTIENEN COLORANTES REACTIVOS MEDIANTE EL MÉTODO DE ELECTRO-OXIDACIÓN CON ELECTRODOS DE TITANIO
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Cárdenas Mendoza, Teodardo J., primary, Quinto Sánchez, Maria, additional, Hermoza Guerra, Emilia G., additional, and Uribe Valenzuela, Carmen L., additional
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- 2023
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17. Micro problems with Macro Consequences: Accumulation of Persistent Organic Pollutants and Microplastics in Human Breast Milk and in Human Milk Substitutes
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Caba-Flores, Mario Daniel, primary, Martínez-Valenzuela, Carmen, additional, Cardenas-Tueme, Marcela, additional, and Camacho-Morales, Alberto, additional
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- 2023
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18. Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of KV1.3 and KV1.5 channels
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Peraza, Diego A., primary, Povo-Retana, Adrián, additional, Mojena, Marina, additional, García-Redondo, Ana B., additional, Avilés, Pablo, additional, Boscá, Lisardo, additional, and Valenzuela, Carmen, additional
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- 2023
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19. D242N, a KV7.1 LQTS mutation uncovers a key residue for IKs voltage dependence
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Moreno, Cristina, Oliveras, Anna, Bartolucci, Chiara, Muñoz, Carmen, de la Cruz, Alicia, Peraza, Diego A., Gimeno, Juan R., Martín-Martínez, Mercedes, Severi, Stefano, Felipe, Antonio, Lambiase, Pier D., Gonzalez, Teresa, and Valenzuela, Carmen
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- 2017
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20. NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer's clinical syndrome: the ATHENEA randomized clinical trial.
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Sosa, Saily, Bringas, Giosmany, Urrutia, Nelky, Peñalver, Ana Ivis, López, Danay, González, Evelio, Fernández, Ana, Hernández, Zenaida Milagros, Viña, Ariel, Peña, Yamile, Batista, Juan Felipe, Valenzuela, Carmen, León, Kalet, Crombet, Tania, Rodríguez, Teresita, Pérez, Leslie, on behalf of the ATHENEA Investigators, Álvarez, Yolanda, Rodríguez, Madelín, and Vázquez, Nairim
- Subjects
ALZHEIMER'S disease ,RECOMBINANT erythropoietin ,CLINICAL trials ,SIALIC acids ,ACTIVITIES of daily living - Abstract
Background: NeuroEPO plus is a recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life due to its low sialic acid content. NeuroEPO plus prevents oxidative damage, neuroinflammation, apoptosis and cognitive deficit in an Alzheimer's disease (AD) models. The aim of this study was to assess efficacy and safety of neuroEPO plus. Methods: This was a double-blind, randomized, placebo-controlled, phase 2–3 trial involving participants ≥ 50 years of age with mild-to-moderate AD clinical syndrome. Participants were randomized in a 1:1:1 ratio to receive 0.5 or 1.0 mg of neuroEPO plus or placebo intranasally 3 times/week for 48 weeks. The primary outcome was change in the 11-item cognitive subscale of the AD Assessment Scale (ADAS-Cog11) score from baseline to 48 weeks (range, 0 to 70; higher scores indicate greater impairment). Secondary outcomes included CIBIC+, GDS, MoCA, NPI, Activities of Daily Living Scales, cerebral perfusion, and hippocampal volume. Results: A total of 174 participants were enrolled and 170 were treated (57 in neuroEPO plus 0.5 mg, 56 in neuroEPO plus 1.0 mg and 57 in placebo group). Mean age, 74.0 years; 121 (71.2%) women and 85% completed the trial. The median change in ADAS-Cog11 score at 48 weeks was −3.0 (95% CI, −4.3 to −1.7) in the 0.5 mg neuroEPO plus group, −4.0 (95% CI, −5.9 to −2.1) in the 1.0 mg neuroEPO plus group and 4.0 (95% CI, 1.9 to 6.1) in the placebo group. The difference of neuroEPO plus 0.5 mg vs. placebo was 7.0 points (95% CI, 4.5–9.5) P = 0.000 and between the neuroEPO plus 1.0 mg vs. placebo was 8.0 points (95% CI, 5.2–10.8) P = 0.000. NeuroEPO plus treatment induced a statistically significant improvement in some of clinical secondary outcomes vs. placebo including CIBIC+, GDS, MoCA, NPI, and the brain perfusion. Conclusions: Among participants with mild-moderate Alzheimer's disease clinical syndrome, neuroEPO plus improved the cognitive evaluation at 48 weeks, with a very good safety profile. Larger trials are warranted to determine the efficacy and safety of neuroEPO plus in Alzheimer's disease. Trial registration: https://rpcec.sld.cu Identifier: RPCEC00000232. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Preterm Delivery in Obese Mothers Predicts Tumor Necrosis Factor-ɑ Levels in Breast Milk.
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Caba-Flores, Mario Daniel, Cardenas-Tueme, Marcela, Viveros-Contreras, Rubí, Martínez-Valenzuela, Carmen, Zurutuza-Lorméndez, Jorge Iván, Ortiz-López, Roció, Cruz-Carrillo, Gabriela, Kuri, Juan Gerardo Neme, Morales, David Huerta, Ramos, Samantha Ponce, Bustos, Edith Nava, and Camacho-Morales, Alberto
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- 2023
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22. CIGB-300: A Promising Anti-Casein Kinase 2 (CK2) Peptide for Cancer Targeted Therapy
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Perea, Silvio E., Perera, Yasser, Baladrón, Idania, González, Lidia, Benavent, Fernando, Fariña, Hernán G., García, Idrián, Rodríguez, Arielis, Reyes, Vilcy, García, Yanelda, Gómez, Roberto, Alonso, Daniel F., Valenzuela, Carmen, Dhalla, Naranjan S., Series editor, Ahmed, Khalil, editor, Issinger, Olaf-Georg, editor, and Szyszka, Ryszard, editor
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- 2015
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23. Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction
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Paz-García, Marta, primary, Povo-Retana, Adrián, additional, Jaén, Rafael I., additional, Prieto, Patricia, additional, Peraza, Diego A., additional, Zaragoza, Carlos, additional, Hernandez-Jimenez, Macarena, additional, Pineiro, David, additional, Regadera, Javier, additional, García-Bermejo, María L., additional, Rodríguez-Serrano, E. Macarena, additional, Sánchez-García, Sergio, additional, Moro, María A., additional, Lizasoaín, Ignacio, additional, Delgado, Carmen, additional, Valenzuela, Carmen, additional, and Boscá, Lisardo, additional
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- 2023
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24. IQM-22110, a new selective inhibitor of KChIP3 and its electrophysiological effects on Kv4.3, Kv4.3/KChIP3 and Kv4.3/KChIP2 currents
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Socuéllamos, Paula G., primary, de Benito-Bueno, Angela, additional, Ropero, Maria, additional, Diez, Sara, additional, Elizalde, Pablo, additional, Bonache, M. Angeles, additional, Viedma, Carmen, additional, Martín-Martínez, Mercedes, additional, Gutiérrez-Rodríguez, Marta, additional, and Valenzuela, Carmen, additional
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- 2023
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25. Pharmacology of cardiac potassium channels
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Tamargo Menéndez, Juan, Caballero Collado, Ricardo, Gómez García, Ricardo, Valenzuela, Carmen, Delpón Mosquera, María Eva, Tamargo Menéndez, Juan, Caballero Collado, Ricardo, Gómez García, Ricardo, Valenzuela, Carmen, and Delpón Mosquera, María Eva
- Abstract
Cardiac K+ channels are membrane-spanning proteins that allow the passive movement of K+ ions across the cell membrane along its electrochemical gradient. They regulate the resting membrane potential, the frequency of pacemaker cells and the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters and hormones and class III antiarrhythmic drugs that prolong the action potential duration (APD) and refractoriness and have been found effective to prevent/suppress cardiac arrhythmias. In the human heart, K+ channels include voltage-gated channels, such as the rapidly activating and inactivating transient outward current (Ito1), the ultrarapid (IKur), rapid (IKr) and slow (IKs) components of the delayed rectifier current and the inward rectifier current (IK1), the ligand-gated channels, including the adenosine triphosphate-sensitive (IKATP) and the acetylcholine-activated (IKAch) currents and the leak channels. Changes in the expression of K+ channels explain the regional variations in the morphology and duration of the cardiac action potential among different cardiac regions and are influenced by heart rate, intracellular signalling pathways, drugs and cardiovascular disorders. A progressive number of cardiac and noncardiac drugs block cardiac K+ channels and can cause a marked prolongation of the action potential duration (i.e. an acquired long QT syndrome, LQTS) and a distinct polymorphic ventricular tachycardia termed torsades de pointes. In addition, mutations in the genes encoding IKr (KCNH2/KCNE2) and IKs (KCNQ1/KCNE1) channels have been identified in some types of the congenital long QT syndrome. This review concentrates on the function, molecular determinants, regulation and, particularly, on the mechanism of action of drugs modulating the K+ channels present in the sarcolemma of human cardiac myocytes that contribute to the different phases of the cardiac action potenti, Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub
- Published
- 2023
26. Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of Kv1.3 and Kv1.5 channels
- Author
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Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Comunidad de Madrid, PharmaMar, Peraza, Diego A., Povo-Retana, Adrián, Mojena, Marina, García-Redondo, Ana B., Avilés, Pablo, Boscá, Lisardo, Valenzuela, Carmen, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Comunidad de Madrid, PharmaMar, Peraza, Diego A., Povo-Retana, Adrián, Mojena, Marina, García-Redondo, Ana B., Avilés, Pablo, Boscá, Lisardo, and Valenzuela, Carmen
- Abstract
Immune cells have an important role in the tumor-microenvironment. Macrophages may tune the immune response toward inflammatory or tolerance pathways. Tumor-associated macrophages (TAM) have a string of immunosuppressive functions and they are considered a therapeutic target in cancer. This study aimed to analyze the effects of trabectedin, an antitumor agent, on the tumor-microenvironment through the characterization of the electrophysiological and molecular phenotype of macrophages. Experiments were performed using the whole-cell configuration of the patch-clamp technique in resident peritoneal mouse macrophages. Trabectedin does not directly interact with KV1.5 and KV1.3 channels, but their treatment (16 h) with sub-cytotoxic concentrations of trabectedin increased their KV current due to an upregulation of KV1.3 channels. In vitro generated TAM (TAMiv) exhibited an M2-like phenotype. TAMiv generated a small KV current and express high levels of M2 markers. K+ current from TAMs isolated from tumors generated in mice is a mixture of KV and KCa, and in TAM isolated from tumors generated in trabectedin-treated mice, the current is mostly driven by KCa. We conclude that the antitumor capacity of trabectedin is not only due to its effects on tumor cells, but also to the modulation of the tumor microenvironment, due, at least in part, to the modulation of the expression of different macrophage ion channels.
- Published
- 2023
27. IQM-22110, a new selective inhibitor of KChIP3 and its electrophysiological effects on Kv4.3, Kv4.3/KChIP3 and Kv4.3/KChIP2 currents
- Author
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Socuéllamos, Paula G., de Benito-Bueno, A., Ropero, M., Díez, S., Elizalde, P., Bonache de Marcos, María Ángeles, Viedma, Carmen, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, Valenzuela, Carmen, Socuéllamos, Paula G., de Benito-Bueno, A., Ropero, M., Díez, S., Elizalde, P., Bonache de Marcos, María Ángeles, Viedma, Carmen, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, and Valenzuela, Carmen
- Abstract
Kv4 channels generate rapidly activating and inactivating outward currents responsible for the repolarization of both cardiac and neuronal action potentials through ITO (transient outward current) and IA (A-type Kþ current), respectively. Kv4 dysfunctions have been identified in both cardiac and neuronal diseases (Brugada syndrome, atrial fibrillation, epilepsy or Alzheimer’s disease). However, Kv4 channels need to assemble with regulatory subunits to fully reproduce ITO and IA currents. Among them, we will focus on KChIPs (potassium channel interacting proteins), being KChIP3 predominant in the brain and KChIP2 in both brain and heart. The assembly of these regulatory subunits not only modulates the biophysical properties of the channel, but also its pharmacology. For this reason, we have analysed the electrophysiological effects of IQM-22110 (a novel KChIP3 ligand) on the currents generated by Kv4.3, Kv4.3/KChIP3 and Kv4.3/KChIP2 channels. CHO cells were transiently transfected, and the potassium currents were recorded using the whole-cell patchclamp technique. Our results indicate that IQM-22110 exerts differential effects on these currents, being the concentration-dependence of inhibition modified, exhibiting a biphasic curve when KChIP3 is present, thus suggesting two binding sites for IQM-22110 in this complex. With molecular dynamics and site-directed mutagenesis, we have identified the binding pocket corresponding to the high affinity site. Also, we have demonstrated that IQM-22110 binds to the closed-active state of the channel. In this study: i) IQM-22110 has proven to be a selective inhibitor of Kv4.3/KChIP3 at low concentrations, and ii) a new binding pocket for selective KChIP3/Kv4.3 ligands has been identified.
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- 2023
28. Geomorphology of The Northern and Southern Continental Margins of The Iberian Peninsula: Quaternary Interplay of Tectonics and Sedimentation
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Ercilla, Gemma, Galindo Zaldivar, Jesús, Juan Valenzuela, Carmen, Estrada, Ferran, Madarieta-Txurruka, Asier, Tendero Salmerón, Vicente, Casas, David, Vázquez Garrido, Juan-Tomás, Teixeira, Manuel, González Castillo, Lourdes, Ercilla, Gemma, Galindo Zaldivar, Jesús, Juan Valenzuela, Carmen, Estrada, Ferran, Madarieta-Txurruka, Asier, Tendero Salmerón, Vicente, Casas, David, Vázquez Garrido, Juan-Tomás, Teixeira, Manuel, and González Castillo, Lourdes
- Abstract
Geomorphic evolution of tectonically active continental margins is the result of the interplay of deformation and sedimentary structures. Iberian Peninsula, located in the present-day NW-SE convergent Eurasia-Africa plate boundary, is mainly deformed in the northern Cantabrian margin (NE Atlantic) and in the southern, both Alboran and Gulf of Vera margins (SW Mediterranean). These margins develop elongated highs and basins roughly parallel to the margins. Moreover, faults and volcanic structures affect the southern Iberia margin. All these deformation structures are responsible for the regional configuration and physiographic components of the margin, seafloor topography, as well as entry points of sediment and pathways of the alongslope (bottom currents) and downslope (mass-transport and gravity flows) sedimentary processes. The deformation structures condition the distribution of deep-sea bottom currents and their sedimentary geomorphic impact is regionally variable during the Quaternary. Contourite features are dominant in the Alboran Sea to the extent that their distribution conditions the physiography. This significant action of bottom currents is linked to the semi-enclosed basin configuration that favours the confinement of the Mediterranean waters. Contrasting, in the Cantabrian and Aguilas open margins, bottom currents are topographically steered by the highs and form local contourite features. Deformation structures also influence the downslope sedimentary processes. Mass-transport and sediment gravity flow features are mostly shaping the Cantabrian and Gulf of Vera margins during the Quaternary. Their occurrence is related to the overstepping or tectonic tilting of the margins, shelf-indenting canyons and narrow shelves. Contrasting, those features are less extended in the Alboran Sea, where their formation is related to seismicity, overstepping of highs, fluid dynamics and turbidite systems. These results indicate that the regional tectonic style of defo
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- 2023
29. Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function
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Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), European Molecular Biology Laboratory, Vera-Zambrano, Alba, Baena-Nuevo, M., Rinné, Susanne, Villegas-Esguevillas, Marta, Barreira, Bianca, Telli, Gokcen, Benito-Bueno, Ángela de, Blázquez, J. A., Climent, Belén, Pérez-Vizcaíno, Francisco, Valenzuela, Carmen, Decher, Niels, González, Teresa, Cogolludo, Angel, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), European Molecular Biology Laboratory, Vera-Zambrano, Alba, Baena-Nuevo, M., Rinné, Susanne, Villegas-Esguevillas, Marta, Barreira, Bianca, Telli, Gokcen, Benito-Bueno, Ángela de, Blázquez, J. A., Climent, Belén, Pérez-Vizcaíno, Francisco, Valenzuela, Carmen, Decher, Niels, González, Teresa, and Cogolludo, Angel
- Abstract
KV1.5 channels are key players in the regulation of vascular tone and atrial excitability and their impairment is associated with cardiovascular diseases including pulmonary arterial hypertension (PAH) and atrial fibrillation (AF). Unfortunately, pharmacological strategies to improve KV1.5 channel function are missing. Herein, we aimed to study whether the chaperone sigma-1 receptor (S1R) is able to regulate these channels and represent a new strategy to enhance their function. By using different electrophysiological and molecular techniques in X. laevis oocytes and HEK293 cells, we demonstrate that S1R physically interacts with KV1.5 channels and regulate their expression and function. S1R induced a bimodal regulation of KV1.5 channel expression/activity, increasing it at low concentrations and decreasing it at high concentrations. Of note, S1R agonists (PRE084 and SKF10047) increased, whereas the S1R antagonist BD1047 decreased, KV1.5 expression and activity. Moreover, PRE084 markedly increased KV1.5 currents in pulmonary artery smooth muscle cells and attenuated vasoconstriction and proliferation in pulmonary arteries. We also show that both KV1.5 channels and S1R, at mRNA and protein levels, are clearly downregulated in samples from PAH and AF patients. Moreover, the expression of both genes showed a positive correlation. Finally, the ability of PRE084 to increase KV1.5 function was preserved under sustained hypoxic conditions, as an in vitro PAH model. Our study provides insight into the key role of S1R in modulating the expression and activity of KV1.5 channels and highlights the potential role of this chaperone as a novel pharmacological target for pathological conditions associated with KV1.5 channel dysfunction.
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- 2023
30. Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension
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Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Commission, European Research Council, Barts Charity, Díaz del Campo, Lucía S., García-Redondo, Ana B., Rodríguez, Cristina, Zaragoza, Carlos, Duro-Sánchez, Santiago, Palmas, Francesco, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Peraza, Diego A., Rodrigues-Díez, Raquel, Valenzuela, Carmen, Dalli, Jesmond, Salaices, Mercedes, Briones, Ana M., Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Commission, European Research Council, Barts Charity, Díaz del Campo, Lucía S., García-Redondo, Ana B., Rodríguez, Cristina, Zaragoza, Carlos, Duro-Sánchez, Santiago, Palmas, Francesco, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Peraza, Diego A., Rodrigues-Díez, Raquel, Valenzuela, Carmen, Dalli, Jesmond, Salaices, Mercedes, and Briones, Ana M.
- Abstract
[Background]: Resolution of inflammation is orchestrated by specialized proresolving lipid mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension., [Methods:]: Aorta, small mesenteric arteries, heart, and peritoneal macrophages were taken from C57BL/6J mice, infused or not with angiotensin II (AngII; 1.44 mg/kg/day, 14 days) in presence or absence of resolvin D2 (RvD2) (100 ng/mice, every second day) starting 1 day before or 7 days after AngII infusion., [Results]: Enzymes and receptors involved in SPMs biosynthesis and signaling were increased in aorta or heart from AngII-infused mice. We also observed a differential regulation of SPMs in heart from these mice. Preventive treatment with RvD2 partially avoided AngII-induced hypertension and protected the heart and large and small vessels against functional and structural alterations induced by AngII. RvD2 increased the availability of vasoprotective factors, modified SPMs profile, decreased cardiovascular fibrosis, and increased the infiltration of pro-resolving macrophages. When administered in hypertensive animals with established cardiovascular damage, RvD2 partially improved cardiovascular function and structure, decreased fibrosis, reduced the infiltration of neutrophils, and shifted macrophage phenotype toward a pro-resolving phenotype., [Conclusions]: There is a disbalance between proinflammatory and resolution mediators in hypertension. RvD2 protects cardiovascular function and structure when administered before and after the development of hypertension by modulating vascular factors, fibrosis and inflammation. Activating resolution mechanisms by treatment with RvD2 may represent a novel therapeutic strategy for the treatment of hypertensive cardiovascular disease.
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- 2023
31. Targeting the neuronal calcium sensor DREAM with small-molecules for Huntington’s disease treatment
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Lopez-Hurtado, Alejandro, Peraza, Diego A., Cercos, Pilar, Lagartera, Laura, Gonzalez, Paz, Dopazo, Xose M., Herranz, Rosario, Gonzalez, Teresa, Martin-Martinez, Mercedes, Mellström, Britt, Naranjo, Jose R., Valenzuela, Carmen, and Gutierrez-Rodriguez, Marta
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- 2019
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32. Materiales textiles antimicronianos con protección a la radiación UV y métodos de funcionalización para la obtención de los mismos
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Amesquita Amesquita, Manuel Jesus, Castro Basurto, Flavia Vanessa, Gomez León, Monica Marcela, Maurtua Torres, Dora Jesus, Romaan Mendoza, Luz Esmeralda, Uribe Valenzuela, Carmen Luisa, Universidad Peruana Cayetano Heredia, and Universidad Nacional de Ingeniería
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D01F 1/00 ,purl.org/pe-repo/ocde/ford#2.05.06 [https] ,D06M 23/08 ,D06M 11/00 ,Antimicrobiano ,radiación UV ,D06M 10/10 - Abstract
La presente invención se refiere a materiales textiles fabricados a partir de fibra de algodón funcionalizada con nanopartículas de óxidos semiconductores que están distribuidas de forma homogénea en el material textil, los cuales le confieren doble funcionalidad de ser antimicrobiano y de protección a la radiación UV; la presente invención también se refiere a los métodos de funcionalización para la obtención de dichos materiales textiles. Vigente
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- 2022
33. Expression Analysis of miRNAs and Their Potential Role as Biomarkers for Prostate Cancer Detection
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Bergez-Hernández, Fernando, primary, Arámbula-Meraz, Eliakym, additional, Alvarez-Arrazola, Marco, additional, Irigoyen-Arredondo, Martín, additional, Luque-Ortega, Fred, additional, Martínez-Camberos, Alejandra, additional, Cedano-Prieto, Dora, additional, Contreras-Gutiérrez, José, additional, Martínez-Valenzuela, Carmen, additional, and García-Magallanes, Noemí, additional
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- 2022
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34. Applying the Global Monitoring Plan and analysis of POPs results in atmospheric air in Mexico (2017–2018)
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Martínez Valenzuela, Carmen, primary, Gavilán García, Arturo, additional, Conde Avila, Victoria, additional, Barrientos Alemán, Dolores, additional, Apodaca Avalos, Marisa, additional, Luna Valdez, José Guadalupe, additional, Castro Carranza, Gabriel, additional, and Masías Ambríz, Luis Omar, additional
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- 2022
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35. Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2
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de Benito-Bueno, Angela, primary, Socuellamos, Paula G., additional, Merinero, Yaiza G., additional, Cercos, Pilar, additional, Izquierdo, Carolina, additional, Daniel-Mozo, Miguel, additional, Marín-Olivero, Irene, additional, Perez-Lara, Angel, additional, Gonzalez-Vera, Juan A., additional, Orte, Angel, additional, Albert, Armando, additional, Martin-Martinez, Mercedes, additional, Gutierrez-Rodriguez, Marta, additional, and Valenzuela, Carmen, additional
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- 2022
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36. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease
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Naranjo, Jose R., Zhang, Hongyu, Villar, Diego, Gonzalez, Paz, Dopazo, Xose M., Moron-Oset, Javier, Higueras, Elena, Oliveros, Juan C., Arrabal, Maria D., Prieto, Angela, Cercos, Pilar, Gonzalez, Teresa, De la Cruz, Alicia, Casado-Vela, Juan, Rabano, Alberto, Valenzuela, Carmen, Gutierrez-Rodriguez, Marta, Li, Jia-Yi, and Mellstrom, Britt
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Huntington's chorea -- Analysis -- Genetic aspects -- Development and progression ,Cellular signal transduction -- Health aspects -- Genetic aspects ,Transcription factors -- Health aspects ,Health care industry - Abstract
Deregulated protein and [Ca.sup.2+] homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional [Ca.sup.2+]-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD., Introduction Huntington's disease (HD) is a progressive neurodegenerative disorder for which there is no cure, caused by the expansion of CAG triplets in the huntingtin (HTT) gene. As in other [...]
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- 2016
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37. Study of kv4.3 channelosome: novel kchip2 ligands as pharmacological tools
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Martinez-Salas, P., Viedma-Barba, C., Benito-Bueno, Ángela de, Socuéllamos, Paula G., Daniel-Mozo, M., Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), and Consejo Superior de Investigaciones Científicas (España)
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KV4.3 channelosome ,KChIP2 ligands ,Atrial fibrillation - Abstract
Trabajo presentado en el VIII Symposia of medicinal chemistry young researchers, celebrado en Barcelona (España) el 22 de julio de 2022., Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Within the heart, KV4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when KV4.3 assembles with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF), the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. Novel KChIP2 ligands could be a useful pharmacological tool to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this communication, we will describe a multidisciplinary approach that, starting with a structure-based virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands., PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/AEI/ 10.13039/501100011033 and by “ESF Investing in your future”.
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- 2022
38. Development of pharmacological tools to study the kv4.3 channelosome in atrial fibrillation
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Viedma-Barba, C., Sandin, P., Bonache de Marcos, María Ángeles, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), and Consejo Superior de Investigaciones Científicas (España)
- Abstract
Resumen del trabajo presentado en el XX National Meeting of the Spanish Society of Medicinal Chemistry, celebrado en Santiago de Compostela (España) del 19 al 22 de junio de 2022., Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions, such as smooth muscle contraction or secretion of hormones. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3 and its role in atrial fibrillation (AF). KV4.3 channel is expressed in smooth muscle, heart and brain. Its activation generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current). KV4.3 plays a key role in AF, the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] To reproduce the ITO currents, KV4.3 channels need to assemble with other subunits, forming channelosome. KChIPs (Potassium Channel Interacting Proteins), which belong to the calcium binding protein superfamily, forms the KV4.3 channelosome, along with other proteins.[3] To study the complex interaction of KV4.3 channelosome and the development of modulators, the interplay of different techniques is central to advance knowledge. In this regard, the development of novel KChIPs modulators and fluorescent biosensors constitutes invaluable pharmacological tools to unravel the KV4 channelosome and its role in AF.[3] In this communication, we will describe preliminary results towards the identification of new pharmacological tools to study the KChIPs/KV4 interaction., This work was supported by the projects: PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 funded by MCIN/ AEI /10.13039/501100011033; and the projects PIE202180E073 and 2019AEP148 funded by CSIC. C. Viedma Barba holds the grant PRE2020-093542 and M. Valencia holds the grant PRE2020-093950, both funded by MCIN/AEI/10.13039/501100011033. A. Pérez-Lara holds the grant RYC2018-023837-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”.
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- 2022
39. New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati
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Viedma-Barba, C., Martinez-Salas, P., Benito-Bueno, Ángela de, Socuéllamos, Paula G., Marín-Olivero, Irene, Daniel-Mozo, M., Pérez-Lara, Ángel, González-Vera, Juan A., Orte, Angel, Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), and Consejo Superior de Investigaciones Científicas (España)
- Abstract
Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022., Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands., PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future”
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- 2022
40. Electrophysiological effects of IQM-266 on Itof. Role of cardiac beta subunits
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Benito-Bueno, Ángela de, Socuéllamos, Paula G., Cercós, Pilar, Izquierdo García, Carolina, Martín-Martínez, Mercedes, Delgado, Carmen, Gutiérrez-Rodríguez, Marta, Valenzuela, Carmen, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, and Consejo Superior de Investigaciones Científicas (España)
- Abstract
Trabajo presentado en el VIII Congreso Red Española de Canales Sónicos, celebrado en Alicante (España) del 24 al 27 de mayo de 2022., The transient outward potassium current (Itof), responsible for the repolarization of cardiac action potential, is generated by the activation of KV4 channels assembled with KChIP2 and other accessory subunits, such as DPP6 and KCNE2. To test the hypothesis that these subunits modify 18 VIII Congreso Red Española de Canales Iónicos the pharmacological response of the channel, we have analyzed the electrophysiological efects of IQM-266 on the currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6, KV4.3/KChIP2/KCNE2 channels and on the total I K and I tof in cardiac myocytes. CHO cells were transiently transfected (KV4.3/KChIP2, KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using the whole-cell patch-clamp technique. In mice cardiac myocytes, potassium currents were recorded by using the perforated patch-clamp technique. Our results indicate that IQM-266 exerts an activating efect on the I K and I tof peak amplitude in cardiac myocytes. To decipher whichbeta subunits were involved in these efects, IQM-266 was studied in CHO cells transfected with the above-mentioned cDNAs. IQM-266, at 3 μM, induced an increase in the KV4.3/KChIP2 current charge, which augmented in the presence of DPP6, whereas it was abolished when KCNE2 was expressed. However, IQM-266 decreased the peak amplitude in transfected cells. In this study we concluded that: i) IQM-266 is a new activator of the I tof in mice cardiac myocytes, ii) DPP6 and KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266, and iii) the presence of either DPP6 or KCNE2 is not enough to reproduce the activator efect observed when IQM-266 was tested on Ito recorded from mouse ventricular myocytes., Grants SAF2016-75021-R, RTI2018-097189-B-C22 funded by MCIN/AEI/10.13039/501100011033 and by ¿ERDF A way of making Europe¿; Grants PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-113238RB-I00 funded by MCIN/AEI/ 10.13039/501100011033; Grant CB/11/00222 funded by ISCIII CIBERCV; Grants PIE202180E073 and 2019AEP148 funded by CSIC. Grants BES-2017-080184, BES-2010-036573 and FPU17/02731 funded by MCIN/AEI/10.13039/501100011033 and by ¿ESF Investing in your future¿.
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- 2022
41. Breast Milk and the Importance of Chrononutrition
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Caba-Flores, Mario Daniel, primary, Ramos-Ligonio, Angel, additional, Camacho-Morales, Alberto, additional, Martínez-Valenzuela, Carmen, additional, Viveros-Contreras, Rubí, additional, and Caba, Mario, additional
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- 2022
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42. Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers
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Cabrales, Ania, Gil, Jeovanis, Fernández, Eduardo, Valenzuela, Carmen, Hernández, Francisco, García, Idrián, Hernández, Ariadna, Besada, Vladimir, Reyes, Osvaldo, Padrón, Gabriel, Berlanga, Jorge, Guillén, Gerardo, and González, Luis Javier
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- 2013
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43. Understanding the complex geomorphology of a deep sea area affected by continental tectonic indentation: the case of the Gulf of Vera (Western Mediterranean)
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Galindo-Zaldívar, J., Estrada, F., Valencia, J., Juan-Valenzuela, Carmen, Casas, D., Alonso, B., Comas, M.C., Tendero-Salmerón, V., Casalbore, Daniele, Azpiroz-Zabala, M., Bárcenas-Gascón, Patricia, Ceramicola, S., Chiocci, F., Idárraga-García, J., López-González, Nieves, Mata, P., Palomino, Desirée, Rodríguez-García, J.A., Teixeira, M., Nespereira, J., Vázquez, Juan Tomás, Yenes, M., Ercilla, G., Galindo-Zaldívar, J., Estrada, F., Valencia, J., Juan-Valenzuela, Carmen, Casas, D., Alonso, B., Comas, M.C., Tendero-Salmerón, V., Casalbore, Daniele, Azpiroz-Zabala, M., Bárcenas-Gascón, Patricia, Ceramicola, S., Chiocci, F., Idárraga-García, J., López-González, Nieves, Mata, P., Palomino, Desirée, Rodríguez-García, J.A., Teixeira, M., Nespereira, J., Vázquez, Juan Tomás, Yenes, M., and Ercilla, G.
- Abstract
We present a multidisciplinary study of morphology, stratigraphy, sedimentology, tectonic structure, and physical oceanography to report that the complex geomorphology of the Palomares continental margin and adjacent Algerian abyssal plain (i.e., Gulf of Vera, Western Mediterranean), is the result of the sedimentary response to the Aguilas Arc continental tectonic indentation in the Eurasian–Africa plate collision. The inden tation is imprinted on the basement of the margin with elongated metamorphic antiforms that are pierced by igneous bodies, and synforms that accommodate the deformation and create a complex physiography. The basement is partially covered by Upper Miocene deposits sealed by the regional Messinian Erosive Surface characterized by palaeocanyons that carve the modern margin. These deposits and outcropping basement highs are then covered and shaped by Plio-Quaternary contourites formed under the action of the Light Intermediate and Dense Deep Mediterranean bottom currents. Even though bottom currents are responsible for the primary sedimentation that shapes the margin, 97% of this region's seafloor is affected by mass-movements that modified contourite sediments by eroding, deforming, faulting, sliding, and depositing sediments. Mass-movement processes have resulted in the formation of recurrent mass-flow deposits, an enlargement of the submarine canyons and gully incisions, and basin-scale gravitational slides spreading above the Messinian Salinity Crisis salt layer. The Polopo, Aguilas and Gata slides are characterized by an extensional upslope domain that shapes the continental margin, and by a downslope contractional domain that shapes the abyssal plain with diapirs piercing (hemi)pelagites/sheet-like turbidites creating a seafloor dotted by numerous crests. The mass movements were mostly triggered by the interplay of the continental tectonic indentation of the Aguilas Arc with sedimentological factors over time. The indentation, which involves t
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- 2022
44. Deep Sea Sedimentation
- Author
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Ercilla, G, Casas, D, Alonso, B., Estrada, F., Idárraga-García, J., López-González, Nieves, Pedrosa, M., Teixeira, M., Sánchez-Guillamón, Olga, Azpiroz-Zabala, M., Bárcenas-Gascón, Patricia, Chiocci, F.L., García-García, Margarita, Galindo-Zaldívar, J., Geyer, A., Gómez-Ballesteros, María, Juan-Valenzuela, Carmen, Martorelli, E., Mata, M.P., Nespereira, J., Palomino, Desirée, Rueda, José Luis, Vázquez, Juan Tomás, Yenes, M., Ercilla, G, Casas, D, Alonso, B., Estrada, F., Idárraga-García, J., López-González, Nieves, Pedrosa, M., Teixeira, M., Sánchez-Guillamón, Olga, Azpiroz-Zabala, M., Bárcenas-Gascón, Patricia, Chiocci, F.L., García-García, Margarita, Galindo-Zaldívar, J., Geyer, A., Gómez-Ballesteros, María, Juan-Valenzuela, Carmen, Martorelli, E., Mata, M.P., Nespereira, J., Palomino, Desirée, Rueda, José Luis, Vázquez, Juan Tomás, and Yenes, M.
- Abstract
This article offers an overview of the main sedimentary systems defining the geomorphology of deep sea environments from low to high latitudes. Mass-transport deposits, turbidite systems, contourites, volcaniclastic aprons, glacial trough mouth systems, carbonate mounds and other bathyal systems, such as pelagites, hemipelagites, mid-ocean channels and polymetallic mineral deposits, are presented with special attention to their morphology, sediments, processes and controlling factors. The integration of the main systems on the continental margins and adjacent abyssal plains in the North Atlantic and westernmost Mediterranean allows to characterize different sedimentation models.
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- 2022
45. Study of kv4.3 channelosome: novel kchip2 ligands as pharmacological tools
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Martinez-Salas, P., Viedma, Carmen, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Daniel-Mozo, Miguel, Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Martinez-Salas, P., Viedma, Carmen, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Daniel-Mozo, Miguel, Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, and Gutiérrez-Rodríguez, Marta
- Abstract
Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Within the heart, KV4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when KV4.3 assembles with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF), the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. Novel KChIP2 ligands could be a useful pharmacological tool to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this communication, we will describe a multidisciplinary approach that, starting with a structure-based virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.
- Published
- 2022
46. New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Viedma, Carmen, Martinez-Salas, P., Benito-Bueno, Ángela de, Socuéllamos, Paula G., Marín-Olivero, Irene, Daniel-Mozo, Miguel, Pérez-Lara, Ángel, González-Vera, Juan A., Orte, Angel, Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Viedma, Carmen, Martinez-Salas, P., Benito-Bueno, Ángela de, Socuéllamos, Paula G., Marín-Olivero, Irene, Daniel-Mozo, Miguel, Pérez-Lara, Ángel, González-Vera, Juan A., Orte, Angel, Albert, Armando, Martín-Martínez, Mercedes, Valenzuela, Carmen, and Gutiérrez-Rodríguez, Marta
- Abstract
Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.
- Published
- 2022
47. Effects of IQM-110 on Kv1.5/Kvß2.1 channels
- Author
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Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Valencia, María, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Bonache de Marcos, María Ángeles, Viedma, Carmen, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, Valenzuela, Carmen, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Valencia, María, Benito-Bueno, Ángela de, Socuéllamos, Paula G., Bonache de Marcos, María Ángeles, Viedma, Carmen, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, and Valenzuela, Carmen
- Abstract
The outward potassium current IKur is the main responsible of the atrial repolarization process and it is generated by the activation of KV1.5 channels, widely expressed in human atria. It is known that mutations in KCNA5 gene, which induce both gain- and loss-of-function in KV1.5 channel, enhance atrial fibrillation susceptibility. Thus, these channels represent a pharmacological target for the development of antiarrhythmic drugs useful in the treatment of supraventricular arrhythmias. KV1.5 channels assembly with several regulatory subunits such as KVß. It has been described that KVß2.1 interacts with KV1.5. Our research group has demonstrated that the molecule IQM-110 produces electrophysiological effects on the KV1.5. The aim of the present study is to analyze the electrophysiological effects of IQM-110 on KV1.5 channels when it was expressed together with the regulatory subunit KVß2.1. In order to achieve this objective, Ltk- cell line constitutively expressing KVß2.1 and with an induced expression of KV1.5 were used. Currents were recorded using the whole-cell configuration of the patch-clamp technique. The effects of IQM-110 on KV1.5/Kvß2.1 current were concentration-dependent with an IC50 of 166¿M (n=64). This compound at 100¿M produced a time-dependent block, inducing a: 1) faster activation (¿=2.8±0.3 vs. 4.1±0.3 ms, n=10, p<0.01), 2) faster inactivation reducing the slow time constant, (¿slow=3172.6±113.8 vs. 629.1±43.8ms, n=5, p<0.001), and 3) slower deactivation kinetics, (¿slow=73.5±3.5 vs. 115.2±12.1ms and ¿fast=19.5±1.3 vs. 27.9±1.9ms, n=10, p<0.01 and p<0.5 respectively). These results are consistent with an open channel block mechanism. Finally, IQM-110 (100 ¿M) enhanced the degree of use-dependent block of the current (1.7±0.4 vs. 47.7±2.4%, n=5, p<0.001). This phenomenon was explained by a slowing of the recovery process in the presence of IQM-110 (¿r=462.6±94.9 vs. 3545.0±254.1ms, n=5, p<0.001). In summary, IQM-110 modulates KV1.5/KVß2.1 channel
- Published
- 2022
48. Development of pharmacological tools to study the kv4.3 channelosome in atrial fibrillation
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Viedma, Carmen, Sandin, P., Bonache de Marcos, María Ángeles, Martín-Martínez, Mercedes, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Viedma, Carmen, Sandin, P., Bonache de Marcos, María Ángeles, Martín-Martínez, Mercedes, Valenzuela, Carmen, and Gutiérrez-Rodríguez, Marta
- Abstract
Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions, such as smooth muscle contraction or secretion of hormones. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3 and its role in atrial fibrillation (AF). KV4.3 channel is expressed in smooth muscle, heart and brain. Its activation generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current). KV4.3 plays a key role in AF, the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] To reproduce the ITO currents, KV4.3 channels need to assemble with other subunits, forming channelosome. KChIPs (Potassium Channel Interacting Proteins), which belong to the calcium binding protein superfamily, forms the KV4.3 channelosome, along with other proteins.[3] To study the complex interaction of KV4.3 channelosome and the development of modulators, the interplay of different techniques is central to advance knowledge. In this regard, the development of novel KChIPs modulators and fluorescent biosensors constitutes invaluable pharmacological tools to unravel the KV4 channelosome and its role in AF.[3] In this communication, we will describe preliminary results towards the identification of new pharmacological tools to study the KChIPs/KV4 interaction.
- Published
- 2022
49. Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2
- Author
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Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Benito-Bueno, Ángela de, Socuéllamos, Paula G., Merinero, Yaiza G., Cercós, Pilar, Izquierdo García, Carolina, Daniel-Mozo, Miguel, Marín-Olivero, Irene, Pérez-Lara, Ángel, González-Vera, Juan A., Orte, Angel, Albert, Armando, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, Valenzuela, Carmen, Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Benito-Bueno, Ángela de, Socuéllamos, Paula G., Merinero, Yaiza G., Cercós, Pilar, Izquierdo García, Carolina, Daniel-Mozo, Miguel, Marín-Olivero, Irene, Pérez-Lara, Ángel, González-Vera, Juan A., Orte, Angel, Albert, Armando, Martín-Martínez, Mercedes, Gutiérrez-Rodríguez, Marta, and Valenzuela, Carmen
- Abstract
The transient outward potassium current (Itof) is generated by the activation of KV4 chan- nels assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 channels. CHO cells were transiently transfected with cDNAs codifying for different proteins (KV4.3/KChIP2, KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using the whole-cell patch-clamp technique. IQM-266 decreased the maximum peak of KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 currents, slowing their time course of inactivation in a concentration-, voltage-, time- and use-dependent manner. IQM-266 produced an increase in the charge in KV4.3/KChIP2 channels that was intensified when DPP6 was present and abolished in the presence of KCNE2. IQM-266 induced an activation unblocking effect during the applica- tion of trains of pulses to cells expressing KV4.3/KChIP2 and KV4.3/KChIP2/KCNE2, but not in KV4.3/KChIP2/DPP6 channels. Overall, all these results are consistent with a preferential IQM-266 binding to an active closed state of Kv4.3/KChIP2 and Kv4.3/KChIP2/KCNE2 channels, whereas in the presence of DPP6, IQM-266 binds preferentially to an inactivated state. In conclusion, DPP6 and KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266.
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- 2022
50. A novel loss of function mutation of the voltage gated potassium channel Kv10.2 involved in epilepsy and autism
- Author
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Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Galán-Vidal, Jesús, Socuéllamos, Paula G., Baena-Nuevo, M., Contreras, Lizbeth, González, Teresa, Pérez-Poyato, María S., Valenzuela, Carmen, González-Lamuño, Domingo, Gandarillas, Alberto, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Galán-Vidal, Jesús, Socuéllamos, Paula G., Baena-Nuevo, M., Contreras, Lizbeth, González, Teresa, Pérez-Poyato, María S., Valenzuela, Carmen, González-Lamuño, Domingo, and Gandarillas, Alberto
- Abstract
[Background]: Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments. [Results]: We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again. [Conclusions]: By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.
- Published
- 2022
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