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Objective: Current international guidelines recommend home blood pressure (BP) measurement and low sodium and high potassium intakes for the management of hypertension. We hypothesized that increased home BP measurement may result in more effective management of sodium and potassium intakes and BP., Methods: We examined associations of home BP measurement days with changes in the urinary sodium-to-potassium (Na/K) ratio, estimated salt and potassium intakes and BP. We included 209 healthy participants (mean age, 55.9 years; 56.5% women) from a prospective cohort study. We examined 1-year data on self-measured home BP and spot urine samples., Results: Median (interquartile range) days of home BP measurement was 324 (225-358) over 1-year. Baseline mean (SD) Na/K ratio, salt and potassium intakes, morning and evening SBP, and morning and evening DBP were 3.8 (2.3), 8.5 (1.9) g/day, 1833.5 (416.5) mg/day, 120.4 (14.0) mmHg, 118.2 (14.2) mmHg, 79.2 (10.1) mmHg, and 76.2 (10.1) mmHg, respectively. In multivariable-adjusted linear regression , β (standard error) per 10 days increase in number of home BP measurement were -0.031 (0.017) for Na/K ratio, -0.036 (0.015) for salt intake, -1.357 (2.797) for potassium intake, -0.178 (0.064) for morning SBP, -0.079 (0.041) for morning DBP, -0.109 (0.067) for evening SBP and -0.099 (0.045) for evening DBP. Additionally, relationships persisted for men and women, but changes in salt intake were more pronounced among participants taking antihypertensive medication (interaction P = 0.002)., Conclusion: Continuous measurement of home BP may lead not only to self-monitoring of BP, but also to declines in salt intakes and some BP indices., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine whether hospital computerised physician order entry (CPOE) systems contribute to securing intravenous potassium chloride (KCl) prescriptions with reference to the recommendations issued by French healthcare agencies., Methods: We sent a questionnaire to the members of the Association pour le Digital et l'Information en Pharmacie., Results: More than three quarters of the 84 responses received involving 23 CPOE systems indicate that it is possible to: prescribe an ampoule of concentrated potassium chloride 10% 10mL intravenously without any diluents (80%); prescribe 4g of KCl in a bag of 500mL of NaCl 0,9% (98%); prescribe a solution that contains 6 grams of KCl per liter (94%); prescribe the administration of an injectable ampoule orally by means of a free text comment (83%). Nearly half of the responses indicate that it is possible to prescribe: concentrated KCl ampoules as administration solvent (50%); an injectable vial to be administered by oral route (52%)., Conclusion: At least 23 hospital CPOE systems are unable to secure the prescriptions of injectable KCl. This finding lifts the veil on an unthought, namely the role of CPOE systems in securing high-risk medications. In order to solve this problem, it should be mandatory that health information technology vendors pay particular attention to these drugs. With regard to injectable KCl, the utilisation of a dilution vehicle, maximum concentration and maximum infusion flow rate are the first four constraints to be satisfied., (Copyright © 2023. Published by Elsevier Masson SAS.)

Cardiovascular diseases, which are the leading cause of death in Croatia, are linked to the high prevalence of hypertension. Both are associated with high salt intake, which was determined almost two decades ago when Croatian Action on Salt and Health (CRASH) was launched. The main objective of the present study was to evaluate salt, potassium, and iodine intake using a single 24 h urine sample in a random sample of the adult Croatian population and to analyse trends in salt consumption after the CRASH was intensively started., Methods: In this study, we analysed data on 1067 adult participants (mean age 57.12 (SD 13.9), men 35%)., Results: Mean salt and potassium intakes were 8.6 g/day (IQR 6.2-11.2) and 2.8 g/day (IQR 2.1-3.5), respectively, with a sodium-to-potassium ratio of 2.6 (IQR 1.8-3.3). We detected a decrease of 17.6% (2 g/day less) in salt consumption compared with our previous salt-mapping study. However, only 13.7% and 8.9% met the WHO salt and potassium recommended targets of 5 g/day and 3.5 g/day, respectively. Salt intake was higher, and potassium ingestion was lower, in rural vs. urban regions and in continental vs. Mediterranean parts of Croatia. Moderate to severe iodine insufficiency was determined in only 3% of the adult participants., Conclusion: In the last fifteen years, salt consumption has been significantly reduced in the Croatian adult population because of the intensive and broad CRASH program. However, salt intake is still too high, and potassium ingestion is too low. Salt reduction programs are the most cost-effective methods of cardiovascular disease prevention and merit greater consideration by the government and health policy makers.

Potassium ion (K + ) is one of the most essential nutrients for the growth and development of tobacco (Nicotiana tabacum L.), however, the molecular regulation of K + concentration in tobacco remains unclear. In this study, a two-pore K (TPK) channel gene NtTPKa was cloned from tobacco, and NtTPKa protein contains the unique K + selection motif GYGD and its transmembrane region primarily locates in the tonoplast membrane. The expression of NtTPKa gene was significantly increased under low-potassium stress conditions. The concentrations of K + in tobacco were significantly increased in the NtTPKa RNA interference lines and CRISPR/Cas9 knockout mutants. In addition, the transport of K + by NtTPKa was validated using patch clamp technique, and the results showed that NtTPKa channel protein exclusively transported K + in a concentration-dependent manner. Together, our results strongly suggested that NtTPKa is a key gene in maintaining K + homeostasis in tobacco, and it could provide a new genetic resource for increasing the concentration of K + in tobacco., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pyrolysis of animal manure at high temperature is necessary to effectively immobilize heavy metals, while the available phosphorus (P) level in biochar is relatively low, rendering it unsuitable for use as fertilizer. In this study, the pretreatment of swine manure with different potassium (K) sources (KOH, K 2 CO 3 , CH 3 COOK and C 6 H 5 K 3 O 7 ) was conducted to produce a biochar with enhanced P availability and heavy metals immobility. The addition of all K compounds lowered the peak temperature of decomposition of cellulose in swine manure. The percentage of ammonium citrate and formic acid extractable P in biochar increased with K addition compared to undoped biochar, with CH 3 COOK and C 6 H 5 K 3 O 7 showing greater effectiveness than KOH and K 2 CO 3 , however, water- extractable P did not exhibit significant changes. Additionally, the available and dissolved Si increased due to the doping of K, with KOH and K 2 CO 3 having a stronger effect than CH 3 COOK and C 6 H 5 K 3 O 7 . X-Ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) analysis revealed that K addition led to the formation of soluble CaKPO 4 and silicate. In addition, the incorporation of K promoted the transformation of labile copper (Cu) and znic (Zn) into the stable fraction while simultaneously reducing their environmental risk. Our study suggest that the co-pyrolysis of swine manure and organic K represents an effective and valuable method for producing biochar with optimized P availability and heavy metals immobility., (© 2024. The Author(s).)

Hypertension affects one billion people worldwide and is the most common risk factor for cardiovascular disease, yet a comprehensive picture of its underlying genetic factors is incomplete. Amongst regulators of blood pressure is the renal outer medullary potassium (ROMK) channel. While select ROMK mutants are prone to premature degradation and lead to disease, heterozygous carriers of some of these same alleles are protected from hypertension. Therefore, we hypothesized that gain-of-function (GoF) ROMK variants which increase potassium flux may predispose people to hypertension. To begin to test this hypothesis, we employed genetic screens and a candidate-based approach to identify six GoF variants in yeast. Subsequent functional assays in higher cells revealed two variant classes. The first group exhibited greater stability in the endoplasmic reticulum, enhanced channel assembly, and/or increased protein at the cell surface. The second group of variants resided in the PIP 2 -binding pocket, and computational modeling coupled with patch-clamp studies demonstrated lower free energy for channel opening and slowed current rundown, consistent with an acquired PIP 2 -activated state. Together, these findings advance our understanding of ROMK structure-function, suggest the existence of hyperactive ROMK alleles in humans, and establish a system to facilitate the development of ROMK-targeted antihypertensives., Competing Interests: Conflict of interest: The authors declare no conflicts of interest.

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I SK1 - 3 ) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I SK1 - 3 . H 2 O 2 enhanced I SK1 - 3 and ET-1 production. Enhancing I SK1 - 3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Activation of the NLRP3 inflammasome is critical in the inflammatory response to gout. Potassium ion (K + ) efflux mediated by the TWIK2 channel is an important upstream mechanism for NLRP3 inflammasome activation. Therefore, the TWIK2 channel may be a promising therapeutic target for MSU crystal-induced inflammation. In the present study, we investigated the effect of ML335, a known K2P channel modulator, on MSU crystal-induced inflammatory responses and its underlying molecular mechanisms., Methods: By molecular docking, we calculated the binding energies and inhibition constants of five K2P channel modulators (Hydroxychloroquine, Fluoxetine, DCPIB, ML365 and ML335) with TWIK2. Intracellular potassium ion concentration and mitochondrial function were assessed by flow cytometry. The interaction between MARCH5 and SIRT3 was demonstrated by immunoprecipitation and Western blotting assay. MSU suspensions were injected into mouse paw and peritoneal cavity to induce acute gout model., Results: ML335 has the highest binding energy and the lowest inhibition constant with TWIK2 in the five calculated K2P channel modulators. In comparison, among these five compounds, ML335 efficiently inhibited the release of IL-1β from MSU crystal-treated BMDMs. ML335 decreased MSU crystal-induced K + efflux mainly dependent on TWIK2 channel. More importantly, ML335 can effectively inhibit the expression of the mitochondrial E3 ubiquitin ligase MARCH5 induced by MSU crystals, and MARCH5 can interact with the SIRT3 protein. ML335 blocked MSU crystal-induced ubiquitination of SIRT3 protein by MARCH5. In addition, ML335 improved mitochondrial dynamics homeostasis and mitochondrial function by inhibiting MARCH5 protein expression. ML335 attenuated the inflammatory response induced by MSU crystals in vivo and in vitro., Conclusion: Inhibition of TWIK2-mediated K + efflux by ML335 alleviated mitochondrial injury via suppressing March5 expression, suggesting that ML335 may be an effective candidate for the future treatment of gout., (© 2024. The Author(s).)

Diabetes is closely associated with K + disturbances during disease progression and treatment. However, it remains unclear whether K + imbalance occurs in diabetes with normal kidney function. In this study, we examined the effects of dietary K + intake on systemic K + balance and renal K + handling in streptozotocin (STZ)-induced diabetic mice. The control and STZ mice were fed low or high K + diet for 7 days to investigate the role of dietary K + intake in renal K + excretion and K + homeostasis and to explore the underlying mechanism by evaluating K + secretion-related transport proteins in distal nephrons. K + -deficient diet caused excessive urinary K + loss, decreased daily K + balance, and led to severe hypokalemia in STZ mice compared with control mice. In contrast, STZ mice showed an increased daily K + balance and elevated plasma K + level under K + -loading conditions. Dysregulation of the NaCl cotransporter (NCC), epithelial Na + channel (ENaC), and renal outer medullary K + channel (ROMK) was observed in diabetic mice fed either low or high K + diet. Moreover, amiloride treatment reduced urinary K + excretion and corrected hypokalemia in K + -restricted STZ mice. On the other hand, inhibition of SGLT2 by dapagliflozin promoted urinary K + excretion and normalized plasma K + levels in K + -supplemented STZ mice, at least partly by increasing ENaC activity. We conclude that STZ mice exhibited abnormal K + balance and impaired renal K + handling under either low or high K + diet, which could be primarily attributed to the dysfunction of ENaC-dependent renal K + excretion pathway, despite the possible role of NCC. NEW & NOTEWORTHY Neither low dietary K + intake nor high dietary K + intake effectively modulates renal K + excretion and K + homeostasis in STZ mice, which is closely related to the abnormality of ENaC expression and activity. SGLT2 inhibitor increases urinary K + excretion and reduces plasma K + level in STZ mice under high dietary K + intake, an effect that may be partly due to the upregulation of ENaC activity.

Background and Aim: Sepsis-induced acute lung injury (ALI) is a complex and life-threatening condition lacking specific and efficient clinical treatments. Extracellular histones, identified as a novel type of damage-associated molecular patterns, have been implicated in the inflammatory process of ALI. However, further elucidation is needed regarding the precise mechanism through which extracellular histones induce inflammation. The aim of this study was to investigate whether extracellular histones can activate NLRP3 inflammasome-mediated inflammation in alveolar macrophages (AMs) by affecting TWIK2-dependent potassium efflux., Methods and Results: We conducted experiments using cecal ligation and puncture (CLP) C57BL/6 mice and extracellular histone-stimulated LPS-primed MH-S cells. The results demonstrated a significant increase in the levels of extracellular histones in the plasma and bronchoalveolar lavage fluid (BALF) of CLP mice. Furthermore, neutralizing extracellular histone mitigated lung injury and inflammation in CLP-induced ALI mice. In vitro studies confirmed that extracellular histones upregulated the expression of NLRP3 inflammasome activation-related proteins in MH-S cells, and this effect was dependent on increased potassium efflux mediated by the TWIK2 channel on the plasma membrane. Moreover, extracellular histones directly triggered a substantial influx of calcium, leading to increased Rab11 activity and facilitating the trafficking and location of TWIK2 to the plasma membrane., Conclusion: These findings underscore the critical role of extracellular histone-induced upregulation of TWIK2 expression on the plasma membrane of alveolar macrophages (AMs). This upregulation leads to potassium efflux and subsequent activation of the NLRP3 inflammasome, ultimately exacerbating lung inflammation and injury during sepsis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Potassium (K + ), being an essential macronutrient in plants, plays a central role in many aspects. Root growth is highly plastic and is affected by many different abiotic stresses including nutrient deficiency. The Shaker-type K + channel Arabidopsis (Arabidopsis thaliana) K + Transporter 1 (AKT1) is responsible for K + uptake under both low and high external K + conditions. However, the upstream transcription factor of AKT1 is not clear. Here, we demonstrated that the WRKY6 transcription factor modulates root growth to low potassium (LK) stress in Arabidopsis. WRKY6 showed a quick response to LK stress and also to many other abiotic stress treatments. The two wrky6 T-DNA insertion mutants were highly sensitive to LK treatment, whose primary root lengths were much shorter, less biomass and lower K + content in roots than those of wild-type plants, while WRKY6-overexpression lines showed opposite phenotypes. A further investigation showed that WRKY6 regulated the expression of the AKT1 gene via directly binding to the W-box elements in its promoter through EMSA and ChIP-qPCR assays. A dual luciferase reporter analysis further demonstrated that WRKY6 enhanced the transcription of AKT1. Genetic analysis further revealed that the overexpression of AKT1 greatly rescued the short root phenotype of the wrky6 mutant under LK stress, suggesting AKT1 is epistatic to WRKY6 in the control of LK response. Further transcriptome profiling suggested that WRKY6 modulates LK response through a complex regulatory network. Thus, this study unveils a transcription factor that modulates root growth under potassium deficiency conditions by affecting the potassium channel gene AKT1 expression., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Ticks transmit a variety of pathogens, including rickettsia and viruses, when they feed on blood, afflicting humans and other animals. Bioactive components acting on inflammation, coagulation, and the immune system were reported to facilitate ticks' ability to suck blood and transmit tick-borne diseases. In this study, a novel peptide, IstTx, from an Ixodes scapularis cDNA library was analyzed. The peptide IstTx, obtained by recombinant expression and purification, selectively inhibited a potassium channel, TREK-1, in a dose-dependent manner, with an IC 50 of 23.46 ± 0.22 μM. The peptide IstTx exhibited different characteristics from fluoxetine, and the possible interaction of the peptide IstTx binding to the channel was explored by molecular docking. Notably, extracellular acidification raised its inhibitory efficacy on the TREK-1 channel. Our results found that the tick-derived peptide IstTx blocked the TREK-1 channel and provided a novel tool acting on the potassium channel.

The disturbance of potassium current in cardiac myocytes caused by potassium channel dysfunction can lead to cardiac electrophysiological disorders, resulting in associated cardiovascular diseases. The emergence of artificial potassium ion channels opens up a way to replace dysfunctional natural ion channels and cure related diseases. However, bionic potassium ion channels have not been introduced into living cells to regulate cell function. One of the biggest challenges is that when the bionic channel fuses with the cell, it is difficult to control the inserting angle of the bionic potassium channel to ensure its penetration of the entire cell membrane. In nature, the extracellular vesicles can fuse with living cells with a completely preserved structure of vesicle protein. Inspired by this, we developed a vesicle fusion-based bionic porin (VFBP), which integrates bionic potassium ion channels into cardiomyocytes to replace damaged potassium ion channels. Theoretical and experimental results show that the inserted bionic ion channels have a potassium ion transport rate comparable to that of natural ion channels, which can restore the potassium ion outflow in cardiomyocytes and repair the abnormal action potential and excitation-contraction coupling of cardiomyocytes. Therefore, the bionic potassium ion channel system based on membrane fusion is expected to become the research object in many fields such as ultrafast ion transport, transmembrane delivery, and channelopathies treatment.

Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the Arenaviridae family of the Bunyavirales order. LCMV is associated with fatal disease in immunocompromised populations and, as the prototypical arenavirus member, acts as a model for the many highly pathogenic members of the Arenaviridae family, such as Junín, Lassa, and Lujo viruses, all of which are associated with devastating hemorrhagic fevers. To enter cells, the LCMV envelope fuses with late endosomal membranes, for which two established requirements are low pH and interaction between the LCMV glycoprotein (GP) spike and secondary receptor CD164. LCMV subsequently uncoats, where the RNA genome-associated nucleoprotein (NP) separates from the Z protein matrix layer, releasing the viral genome into the cytosol. To further examine LCMV endosome escape, we performed an siRNA screen which identified host cell potassium ion (K + ) channels as important for LCMV infection, with pharmacological inhibition confirming K + channel involvement during the LCMV entry phase completely abrogating productive infection. To better understand the K + -mediated block in infection, we tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z proteins. In contrast, K + channel blockade prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K + as a third LCMV entry requirement. K + did not increase GP-CD164 binding or alter GP-CD164-dependent fusion. Thus, we propose that K + mediates uncoating by modulating NP-Z interactions within the virion interior. These results suggest K + channels represent a potential anti-arenaviral target.IMPORTANCEArenaviruses can cause fatal human disease for which approved preventative or therapeutic options are not available. Here, using the prototypical LCMV, we identified K + channels as critical for arenavirus infection, playing a vital role during the entry phase of the infection cycle. We showed that blocking K + channel function resulted in entrapment of LCMV particles within late endosomal compartments, thus preventing productive replication. Our data suggest K + is required for LCMV uncoating and genome release by modulating interactions between the viral nucleoprotein and the matrix protein layer inside the virus particle., Competing Interests: The authors declare no conflict of interest.

Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material. BmKcug1a-P1 inhibited hKv1.2 and hKv1.3 potassium channels with IC 50 values of 2.12 ± 0.27 μM and 1.54 ± 0.28 μM, respectively. To investigate the influence of N-terminal amino acid loss on the potassium channel inhibiting activities, three analogs (i.e., full-length BmKcug1a, BmKcug1a-P1-D2 and BmKcug1a-P1-D4) of BmKcug1a-P1 were prepared, and their potassium channel inhibiting activities on hKv1.3 channel were verified by whole-cell patch clamp technique. Interestingly, the potassium channel inhibiting activity of full-length BmKcug1a on the hKv1.3 channel was significantly improved compared to its N-terminal degraded form (BmKcug1a-P1), while the activities of two truncated analogs (i.e., BmKcug1a-P1-D2 and BmKcug1a-P1-D4) were similar to that of BmKcug1a-P1. Extensive alanine-scanning experiments identified the bonding interface (including two key functional residues, Asn30 and Arg34) of BmKcug1a-P1. Structural and functional dissection further elucidated whether N-terminal residues of the peptide are located at the bonding interface is important in determining whether the N-terminus significantly influences the potassium channel inhibiting activity of the peptide. Altogether, this research identified a novel N-terminal degraded active peptide, BmKcug1a-P1, from traditional Chinese scorpion medicinal material and elucidated how the N-terminus of peptides influences their potassium channel inhibiting activity, contributing to the functional identification and molecular truncation optimization of full-length and degraded peptides from traditional Chinese scorpion medicinal material Buthus martensii Karsch., (© 2024. The Author(s).)

Aim: To assess the impact of endurance training on skeletal muscle release of H + and K + ., Methods: Nine participants performed one-legged knee extension endurance training at moderate and high intensities (70%-85% of W peak ), three to four sessions·week -1 for 6 weeks. Post-training, the trained and untrained (control) leg performed two-legged knee extension at low, moderate, and high intensities (40%, 62%, and 83% of W peak ) in normoxia and hypoxia (~4000 m). The legs were exercised simultaneously to ensure identical arterial inflow concentrations of ions and metabolites, and identical power output was controlled by visual feedback. Leg blood flow was measured (ultrasound Doppler), and acid-base variables, lactate- and K + concentrations were assessed in arterial and femoral venous blood to study K + and H + release. Ion transporter abundances were assessed in muscle biopsies., Results: Lactate-dependent H + release was similar in hypoxia to normoxia (p = 0.168) and was lower in the trained than the control leg at low-moderate intensities (p = 0.060-0.006) but similar during high-intensity exercise. Lactate-independent and total H + releases were higher in hypoxia (p < 0.05) and increased more with power output in the trained leg (leg-by-power output interactions: p = 0.02). K + release was similar at low intensity but lower in the trained leg during high-intensity exercise in normoxia (p = 0.024) and hypoxia (p = 0.007). The trained leg had higher abundances of Na + /H + exchanger 1 (p = 0.047) and Na + /K + pump subunit α (p = 0.036)., Conclusion: Moderate- to high-intensity endurance training increases lactate-independent H + release and reduces K + release during high-intensity exercise, coinciding with increased Na + /H + exchanger 1 and Na + /K + pump subunit α muscle abundances., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Ultraprocessed foods can be a source of potassium additives. Excess potassium consumption can lead to hyperkalemia. How frequently potassium additives are found in the food supply and how they impact potassium content is not well documented. Using the Branded Product Database, ingredient lists were searched for "potassium" to identify products containing additives. For products listing potassium content, accuracy of potassium content reporting and how potassium content differed with additive use was also assessed. A total of 239,089 products were included, 35,102 (14.7%) contained potassium additives, and 13,685 (5.7%) provided potassium content. Potassium additives were most commonly found in dairy products, supplements, and mixed foods (at 37%, 34%, and 28%, respectively). Potassium additives in mixed foods and vegetables and fruits were associated with 71% and 28% more potassium per serving, respectively (p < 0.01). Potassium content increased by 1874 mg (66%) when a 1-day sample menu compared foods with and without additives. Potassium content of foods with and without additives is not well documented. Potassium additives are prevalent and can be associated with increased potassium content. However, more information is needed to better understand how different additives used in different foods change potassium content., (© 2021 Wiley Periodicals LLC.)

Recent literature reports highlight the importance of the renal outer medullary potassium (ROMK) channel in renal sodium and potassium homeostasis and emphasize the potential impact that ROMK inhibitors could have as a novel mechanism diuretic in heart failure patients. A series of piperazine-based ROMK inhibitors were designed and optimized to achieve excellent ROMK potency, hERG selectivity, and ADME properties, which led to the identification of compound 28 (BMS-986308). BMS-986308 demonstrated efficacy in the volume-loaded rat diuresis model as well as promising in vitro and in vivo profiles and was therefore advanced to clinical development.

Voltage-gated potassium channel 1.3 (Kv1.3) has emerged as a pivotal player in numerous biological processes and pathological conditions, sparking considerable interest as a potential therapeutic target across various diseases. In this review, we present a comprehensive examination of Kv1.3 channels, highlighting their fundamental characteristics and recent advancements in utilizing Kv1.3 inhibitors for treating autoimmune disorders, neuroinflammation, and cancers. Notably, Kv1.3 is prominently expressed in immune cells and implicated in immune responses and inflammation associated with autoimmune diseases and chronic inflammatory conditions. Moreover, its aberrant expression in certain tumors underscores its role in cancer progression. While preclinical studies have demonstrated the efficacy of Kv1.3 inhibitors, their clinical translation remains pending. Molecular imaging techniques offer promising avenues for tracking Kv1.3 inhibitors and assessing their therapeutic efficacy, thereby facilitating their development and clinical application. Challenges and future directions in Kv1.3 inhibitor research are also discussed, emphasizing the significant potential of targeting Kv1.3 as a promising therapeutic strategy across a spectrum of diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Stable and entrainable physiological circadian rhythms are crucial for overall health and well-being. The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, consists of diverse neuron types that collectively generate a circadian profile of electrical activity. However, the mechanisms underlying the regulation of endogenous neuronal excitability in the SCN remain unclear. Two-pore domain potassium channels (K2P), including TASK-3, are known to play a significant role in maintaining SCN diurnal homeostasis by inhibiting neuronal activity at night. In this study, we investigated the role of TASK-3 in SCN circadian neuronal regulation and behavioural photoentrainment using a TASK-3 global knockout mouse model. Our findings demonstrate the importance of TASK-3 in maintaining SCN hyperpolarization during the night and establishing SCN sensitivity to glutamate. Specifically, we observed that TASK-3 knockout mice lacked diurnal variation in resting membrane potential and exhibited altered glutamate sensitivity both in vivo and in vitro. Interestingly, despite these changes, the mice lacking TASK-3 were still able to maintain relatively normal circadian behaviour.

Klotho regulates many pathways in the aging process, but it remains unclear how it is physiologically regulated. Because Klotho is synthesized, cleaved, and released from the kidney; activates the chief urinary K + secretion channel (ROMK) and stimulates urinary K + secretion, we explored if Klotho protein is regulated by dietary K + and the potassium-regulatory hormone, Aldosterone. Klotho protein along the nephron was evaluated in humans and in wild-type (WT) mice; and in mice lacking components of Aldosterone signaling, including the Aldosterone-Synthase KO (AS-KO) and the Mineralocorticoid-Receptor KO (MR-KO) mice. We found the specific cells of the distal nephron in humans and mice that are chief sites of regulated K + secretion have the highest Klotho protein expression along the nephron. WT mice fed K + -rich diets increased Klotho expression in these cells. AS-KO mice exhibit normal Klotho under basal conditions but could not upregulate Klotho in response to high-K + intake in the K + -secreting cells. Similarly, MR-KO mice exhibit decreased Klotho protein expression. Together, i) Klotho is highly expressed in the key sites of regulated K + secretion in humans and mice, ii) In mice, K + -rich diets increase Klotho expression specifically in the potassium secretory cells of the distal nephron, iii) Aldosterone signaling is required for Klotho response to high K + intake., (© 2024. The Author(s).)

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Potassium (K + )-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K + -dependent signaling pathway in the kidney distal convoluted tubule, coined the K + switch, that couples extracellular K + sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established., Methods: To test the hypothesis that small, physiological changes in plasma K + (P K+ ) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule. The CA-SPAK (constitutively active SPS1-related proline/alanine-rich kinase mice) were compared with control mice over a 4-day P K+ titration (3.8-5.1 mmol) induced by changes in dietary K + . Arterial BP was monitored using radiotelemetry, and renal function measurements, NCC abundance, phosphorylation, and activity were made., Results: As P K+ decreased in control mice, BP progressively increased and became sensitive to dietary NaCl and hydrochlorothiazide, coincident with increased NCC phosphorylation and urinary sodium retention. By contrast, BP in CA-SPAK mice was elevated, resistant to the P K+ titration, and sensitive to hydrochlorothiazide and salt at all P K+ levels, concomitant with sustained and elevated urinary sodium retention and NCC phosphorylation and activity. Thus, genetically locking the switch on drives NaCl sensitivity and prevents the response of BP to potassium., Conclusions: Low K + , common in modern ultraprocessed diets, presses the K + -switch pathway to turn on NCC activity, increasing sodium retention, BP, and salt sensitivity., Competing Interests: Disclosures None.

Salinity stress significantly constrains agricultural productivity and vegetation decline worldwide, particularly in Iran. Potassium, the second most prevalent nutrient in plants, is well known to be essential for cell metabolism. Here, the effects of potassium fertilizer in two biogenic nanoparticles (K-NPs) and conventional (potassium sulfate) forms (0.1 mg/ml) on Melissa officinalis L. under salinity (0, 50, 100, and 150 mM) were investigated. The results demonstrated that stress markers (electrolyte leakage, malondialdehyde, and hydrogen peroxide) increased as salinity levels increased. Plant growth parameters (shoot and root length, fresh and dry weight of shoot and root) and physiological and photosynthetic parameters (stomatal conductance, relative water content, chlorophyll fluorescence, and photosynthetic pigments) were reduced in salinized plants. The highest reduction in fresh weight root, dry weight root, fresh weight shoot, dry weight shoot, root length, and shoot length was recorded under 150 mM NaCl by 30.2%, 51.6%, 30.5%, 24.7%, 26.4%, and 21%, respectively. In contrast, bulk potassium sulfate and K-NPs increased these parameters. Furthermore, K-NPs improved M. officinalis tolerance to NaCl toxicity by enhancing the content of osmolytes such as proline, soluble sugars, and antioxidant enzymes, improving antioxidant contents such as phenols, tannins, anthocyanins, and flavonoids; increasing total protein; and lowering stress markers in plant tissues. Given the results of the physiological, biochemical, and phytochemical parameters obtained from this study, it can be stated that K-NPs, in comparison to the conventional form of potassium fertilizer, exhibit a greater potential to mitigate damages caused by salinity stress in M. officinalis plants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K + (BIC K ) with the highest transport activity among them. The selected BIC K can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BIC K does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BIC K , will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K + transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K + transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BIC K can efficiently simulate natural K + channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K + transport function for the first time. This study found that the potassium transmembrane transport by BIC K significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gain-of-function mutations in the KCNT1 gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor ( 8 ) discovered via a high-throughput screen. Across three distinct regions of the chemotype, we synthesized 58 new analogs and tested each one in a whole-cell automated patch-clamp assay to develop structure-activity relationships for inhibition of SLACK channels. We further evaluated selected analogs for their selectivity versus a variety of other ion channels and for their activity versus clinically relevant SLACK mutants. Selectivity within the series was quite good, including versus hERG. Analog 80 (VU0948578) was a potent inhibitor of WT, A934T, and G288S SLACK, with IC 50 values between 0.59 and 0.71 µM across these variants. VU0948578 represents a useful in vitro tool compound from a chemotype that is distinct from previously reported small molecule inhibitors of SLACK channels.

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In this study, we have used the patch-clamp technique to assess the effects of sertraline on Kv2.1 channels heterologously expressed in HEK-293 cells and on the voltage-gated potassium currents (I Kv ) of Neuro 2a cells, which are predominantly mediated by Kv2.1 channels. Our results reveal that sertraline inhibits Kv2.1 channels in a concentration-dependent manner. The sertraline-induced inhibition was not voltage-dependent and did not require the channels to be open. The kinetics of activation and deactivation were accelerated and decelerated, respectively, by sertraline. Moreover, the inhibition by this drug was use-dependent. Notably, sertraline significantly modified the inactivation mechanism of Kv2.1 channels; the steady-state inactivation was shifted to hyperpolarized potentials, the closed-state inactivation was enhanced and accelerated, and the recovery from inactivation was slowed, suggesting that this is the main mechanism by which sertraline inhibits Kv2.1 channels. Overall, this study provides novel insights into the pharmacological actions of sertraline on Kv2.1 channels, shedding light on the intricate interaction between SSRIs and ion channel function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoporosis is a significant public health concern, particularly in aging populations, leading to fractures, decreased mobility, and reduced quality of life. While calcium and vitamin D have long been recognized as essential for bone health, emerging research suggests that potassium may play a crucial role in maintaining bone density and preventing osteoporosis. This manuscript explores the relationship between potassium and osteoporosis, delving into the mechanisms, epidemiological evidence, and potential therapeutic implications of potassium in bone health. Furthermore, the manuscript discusses the sources of dietary potassium, its impact on bone metabolism, and the future directions in research and clinical practice regarding potassium's role in osteoporosis management., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Although the subject of numerous studies, the associations between dietary sodium, potassium, and the ratio of dietary sodium to potassium with blood pressure are not clear-cut. In addition, there is a paucity of research on these relationships in prospective cohort studies with representation from diverse Hispanic/Latino adults., Objectives: To evaluate the associations between dietary intake of sodium, potassium, and the ratio of dietary sodium to potassium and blood pressure in a diverse sample of Hispanics living in the United States., Methods: This analysis included 11,429 Hispanic/Latino participants of the prospective cohort Hispanic Community Health Study/Study of Latinos recruited between 2008 and 2011 in visit 1 who participated in a follow-up visit in 2014-2017. Dietary sodium and potassium intakes were averaged from 2 interviewer-administered 24-h diet recalls collected at visit 1. At both visits, blood pressure was measured 3 times in a seated position and averaged. We assessed the relationship between dietary sodium, potassium, and the sodium-to-potassium ratio with changes in systolic and diastolic blood pressure using survey-weighted multivariable-adjusted regression models., Results: At visit 1, the mean age was 41 y, and the mean sodium intake was 3203 mg/d. Each 500 mg/d sodium increment in intake was associated with an increase in systolic blood pressure (β: 0.35 [mmHg]; 95% confidence interval: 0.06, 0.63) and diastolic blood pressure (β: 0.45 [mmHg]; 95% confidence interval: 0.08, 0.82). Dietary potassium and the molar ratio of dietary sodium to potassium were not associated with changes in systolic or diastolic blood pressure., Conclusions: Among a large sample of diverse United States Hispanic/Latino adults, higher sodium intake was associated with small increases in systolic blood pressure over 6 y. This research underscores the importance of dietary sodium reduction in maintaining lower blood pressure., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

BeKm-1 is a peptide toxin from scorpion venom that blocks the pore of the potassium channel hERG (K v 11.1) in the human heart. Although individual protein structures have been resolved, the structure of the complex between hERG and BeKm-1 is unknown. Here, we used molecular dynamics and ensemble docking, guided by previous double-mutant cycle analysis data, to obtain an in silico model of the hERG-BeKm-1 complex. Adding to the previous mutagenesis study of BeKm-1, our model uncovers the key role of residue Arg20, which forms three interactions (a salt bridge and hydrogen bonds) with the channel vestibule simultaneously. Replacement of this residue even by lysine weakens the interactions significantly. In accordance, the recombinantly produced BeKm-1 R20K mutant exhibited dramatically decreased activity on hERG. Our model may be useful for future drug design attempts., (© 2024 Federation of European Biochemical Societies.)

Chicory is a food with high nutritional. The use of beneficial elements in plants, such as sodium (Na) and silicon (Si), may be important to mitigate nutritional disorders, such as potassium (K) deficiency, but research is lacking on this topic. The objective was to evaluate the effects of sodium and nano-silicon on the nutritional, physiological, growth, and quality parameters of chicory under K deficiency and sufficiency. We used a concentration for sufficient K (3.0 mmol L -1 ), K-deficiency (1.5 mmol L -1 ), combined with the lack or presence of Na (2.0 mmol L -1 ) and Si (2.0 mmol L -1 ). The experiment was carried out in a greenhouse with six treatments corresponding to K sufficiency, K-sufficiency with Na, K-sufficiency with Si, K deficiency, K-deficiency with Na, and K-deficiency with Si, with six replications. The following growth variables were evaluated: (i) plant height, (ii) stem diameter, (iii) number of leaves, (iv) leaf area, and (v) plant biomass. Potassium and Si contents in the above ground part and K utilization efficiency were assessed, and the accumulation of K, Na, and Si was calculated. The efficiency of the quantum yield of photosystem II (Fv/Fm) and the photosynthetic pigments was determined. Electrolyte leakage index and relative water content, as well as phenolic compounds, ascorbic acid, and leaf firmness index were also determined. We found that supplying nano-Si and Na to a K-deficient nutrient solution increased K accumulation by 60% and 50% and K use efficiency by 79% and 62% compared to plants without supply of those elements. Nano-Si reduced electrolyte leakage, being 41% less than Na in K-deficient chicory. However, when Na was added to a nutrient solution with sufficient potassium, the K use efficiency decreased by 48% compared to sufficient potassium without Na. Under the same condition of sufficient supply of potassium and Na, K accumulation decreased by 20% in chicory compared to sufficient potassium without Na, and the photosynthetic pigments-total chlorophyll and carotenoids-were reduced by 5% and 10%, respectively. Our findings contribute to improve cultivation systems with low supply of K as the supply of Na and nano-Si mitigates the damage caused to the metabolism of chicory under K deficiency., (© 2024. The Author(s).)

Background and Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (E m ) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative E m is mainly set by two pore domain potassium (K 2P ) channels, of which the TASK-1 has been extensively investigated., Experimental Approach: Ion channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods. Intracellular [Ca 2+ ] was monitored using fluorescent microscopy. Pulmonary BP and vascular tone measurements were also performed ex vivo using a rat PAH model., Key Results: TREK-1 was the most abundantly expressed K 2P in hPASMCs of healthy donors and idiopathic(I) PAH patients. Background K + -current was similar in hPASMCs for both groups and significantly enhanced by the TREK activator ML-335. In donor hPASMCs, siRNA silencing or pharmacological inhibition of TREK-1 caused depolarisation, reminiscent of the electrophysiological phenotype of idiopathic PAH. ML-335 hyperpolarised donor hPASMCs and normalised the E m of IPAH hPASMCs. A close link was found between TREK-1 activity and intracellular Ca 2+ -signalling using a channel activator, ML-335, and an inhibitor, spadin. In the rat, ML-335 relaxed isolated pre-constricted pulmonary arteries and significantly decreased pulmonary arterial pressure in the isolated perfused lung., Conclusions and Implications: These data suggest that TREK-1is a key factor in E m setting and Ca 2+ homeostasis of hPASMC, and therefore, essential for maintenance of a low resting pulmonary vascular tone. Thus TREK-1 may represent a new therapeutic target for PAH., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Voltage-dependent K + (Kv) channels play an important role in restoring the membrane potential to its resting state, thereby maintaining vascular tone. In this study, native smooth muscle cells from rabbit coronary arteries were used to investigate the inhibitory effect of quetiapine, an atypical antipsychotic agent, on Kv channels. Quetiapine showed a concentration-dependent inhibition of Kv channels, with an IC 50 of 47.98 ± 9.46 μM. Although quetiapine (50 μM) did not alter the steady-state activation curve, it caused a negative shift in the steady-state inactivation curve. The application of 1 and 2 Hz train steps in the presence of quetiapine significantly increased the inhibition of Kv current. Moreover, the recovery time constants from inactivation were prolonged in the presence of quetiapine, suggesting that its inhibitory action on Kv channels is use (state)-dependent. The inhibitory effects of quetiapine were not significantly affected by pretreatment with Kv1.5, Kv2.1, and Kv7 subtype inhibitors. Based on these findings, we conclude that quetiapine inhibits Kv channels in both a concentration- and use (state)-dependent manner. Given the physiological significance of Kv channels, caution is advised in the use of quetiapine as an antipsychotic due to its potential side effects on cardiovascular Kv channels., (© 2024 John Wiley & Sons Ltd.)

Previous studies exploring the relationship between dietary potassium and magnesium intake and the risk of type 2 diabetes mellitus (T2DM) have yielded inconsistent results and the lack evidence from rural China. Therefore, we aimed to investigate the association between dietary potassium and magnesium intake and the risk of T2DM in rural China. Data was collected from the Henan Rural Cohort Study in 2017. A validated semi-quantitative food frequency questionnaire assessed dietary potassium and magnesium intake. Logistic regression models were used to calculate odds ratio (ORs) and 95% confidence intervals (CIs) to evaluate the effect of dietary potassium, magnesium and the potassium-magnesium ratio on the risk of T2DM. A total of 38384 individuals were included in the study, and 3616 participants developed T2DM. Logistic regression analysis revealed that the OR (95% CI) of the highest versus dietary potassium and magnesium and potassium-magnesium ratio intakes were 0.67 (0.59, 0.75), 0.76 (0.67, 0.88), and 0.57 (0.50, 0.66), respectively, compared to the subjects with the lowest quartile of intakes. In addition, gender partially influences the relationship between dietary magnesium and T2DM prevalence (P- interaction = 0.042). The group with the highest dietary potassium and dietary magnesium intake had the lowest risk of T2DM, with an OR (95% CI) of 0.63 (0.51-0.77). Dietary potassium and magnesium intake are important modifiable risk factors for T2DM in rural China. Dietary potassium intake > 1.8g/day, dietary magnesium intake > 358.6mg/day and < 414.7mg/day and potassium-magnesium ratio >5.1 should be encouraged to prevent better and manage T2DM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated how membrane thickness and tension modify the gating of KcsA potassium channels when simultaneously varied. The KcsA channel undergoes global conformational changes upon gating: expansion of the cross-sectional area and longitudinal shortening upon opening. Thus, membranes impose differential effects on the open and closed conformations, such as hydrophobic mismatches. Here, the single-channel open probability was recorded in the contact bubble bilayer, by which variable thickness membranes under a defined tension were applied. A fully open channel in thin membranes turned to sporadic openings in thick membranes, where the channel responded moderately to tension increase. Quantitative gating analysis prompted the hypothesis that tension augmented the membrane deformation energy when hydrophobic mismatch was enhanced in thick membranes., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0860.