16 results on '"Langthaler Sonja"'
Search Results
2. Consideration of Kv ion channels as firstorder systems
- Author
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Lozanović Jasmina, Langthaler Sonja, Rienmüller Theresa Margarethe, Polz Mathias, Ziesel Daniel, Schröttner Jörg, and Baumgartner Christian
- Subjects
kv channel ,control engineering ,first order systems ,dynamic behavior ,Medicine - Abstract
This paper discusses possibilities to explain which Kv channels can be considered as first-order systems. This means that the dynamic behavior of these channels can be described with a first-order differential equation and are the most straightforward dynamical systems. For example, a typical first-order system is an RC circuit, and analogously, Kv channels can be considered with the dynamic behavior of first-order systems following RC circuits. This work represents a family of KV channels that can be described as first-order systems, providing an efficient method of ion channel modeling in computational electrophysiology.
- Published
- 2023
- Full Text
- View/download PDF
3. Temperature-induced modulation of the electrophysiological behavior of A549 lung cancer cells
- Author
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Langthaler Sonja, Rienmüller Theresa, Lozanović Šajić Jasmina, and Baumgartner Christian
- Subjects
temperature modulation ,membrane potential ,ion channel kinetics ,oncological hyperthermia ,Medicine - Abstract
Cancer cells typically exhibit altered ion channel expression and membrane potential, wich plays an important role in various processes such as proliferation or apoptosis Hence, therapeutic strategies that modulate ion channel activity or shift the membrane potential prove to be promising for cancer therapy. Since temperature significantly affects ion channel function, deviation from normal body temperture might provide akey factor in electrophysiological progression. In this pilot study, we focused on a first insight into the temperature-induced modulation of A549 cells using an automated patch clamp system. Measurements of 14 cells at hypo-, normo- and hypertermia were accomplished to investigate the temperature-dependent electophysiological behavior. The results revealed that both, temperatures below and above normal body temperature affect the current and potential of A549 cells. In hyperthermia the potential tends to more hyperpolarized values, while conversely, in hypothermic conditions we observer mainly a lower current reponse and thus a depolarization of the membrane potential.
- Published
- 2022
- Full Text
- View/download PDF
4. The Kv10.1 voltage-gated ion channel modeling based on control system theory
- Author
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Lozanović Šajić Jasmina, Langthaler Sonja, and Baumgartner Christian
- Subjects
kv10.1 voltage-gated ion channel ,control systems ,systems identification ,mathematical modeling ,transfer function ,Medicine - Abstract
In this paper, we present a control system theory based modeling approach for the voltage-gated ion-channel Kv10.1 at different temperatures. Kv10.1 is expressed in the central nervous system and the brain of healthy humans. The study of the activity of this ion channel is important, because its activity is associated with the occurrence of cancer in different organs or tissues. According to systems and control theory, the voltage-gated channel Kv10.1 was assumed to be a linear time-invariant system and, as such, exhibits dynamic behavior. The experimental results show that Kv10.1 operates as a first-order model based on the input voltage step protocol and the measured macroscopic ion current output.
- Published
- 2022
- Full Text
- View/download PDF
5. Usability evaluation of a locomotor therapy device considering different strategies
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Langthaler Sonja, Lassnig Alexander, Baumgartner Christian, and Schröttner Jörg
- Subjects
operating safety ,promediks ,usability testing ,use error ,useprob ,Medicine - Abstract
Usability of medical devices is one of the main determining factors in preventing use errors in treatment and strongly correlates to patient safety and quality of treatment. This thesis demonstrates the usability testing and evaluation of a prototype for locomotor therapy of infants. Therefore, based on the normative requirements of the EN 62366, a concept combined of evaluation procedures and assessing methods was created to enable extensive testing and analysis of the different aspects of usability. On the basis of gathered information weak points were identified and appropriate measures were presented to increase the usability and operating safety of the locomotor prototype. The overall outcome showed an usability value of 77.4% and an evaluation score of 6.99, which can be interpreted as “satisfactory”.
- Published
- 2016
- Full Text
- View/download PDF
6. System identification and mathematical modeling of the pandemic spread COVID-19 in Serbia
- Author
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Šajić, Jasmina Lozanović, Langthaler, Sonja, Schröttner, Jörg, and Baumgartner, Christian
- Published
- 2022
- Full Text
- View/download PDF
7. The bioelectric mechanisms of local calcium dynamics in cancer cell proliferation: an extension of the A549 in silico cell model.
- Author
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Langthaler, Sonja, Zumpf, Christian, Rienmüller, Theresa, Shrestha, Niroj, Fuchs, Julia, Zhou, Rui, Pelzmann, Brigitte, Zorn-Pauly, Klaus, Fröhlich, Eleonore, Weinberg, Seth H., and Baumgartner, Christian
- Published
- 2024
- Full Text
- View/download PDF
8. GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A
- Author
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Schratter, Gebhard, Scheruebel, Susanne, Langthaler, Sonja, Ester, Katja, Pelzmann, Brigitte, Ghaffari-Tabrizi-Wizsy, Nassim, Rezania, Simin, Gorischek, Astrid, Platzer, Dieter, Zorn-Pauly, Klaus, Ahammer, Helmut, Prokesch, Andreas, Stanzer, Stefanie, Devaney, Trevor T. J., Schmidt, Kurt, Jahn, Stephan W., Prassl, Ruth, Bauernhofer, Thomas, and Schreibmayer, Wolfgang
- Published
- 2019
- Full Text
- View/download PDF
9. Consequences of somatic mutations of GIRK1 detected in primary malign tumors on expression and function of Gprotein activated, inwardly rectifying, K+ channels.
- Author
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Pelzmann, Brigitte, Hatab, Ahmed, Scheruebel, Susanne, Langthaler, Sonja, Rienmueller, Theresa, Sokolowski, Armin, Gorischek, Astrid, Platzer, Dieter, Zorn-Pauly, Klaus, Jahn, Stephan W., Bauernhofer, Thomas, and Schreibmayer, Wolfgang
- Subjects
SOMATIC mutation ,GAIN-of-function mutations ,LOBULAR carcinoma ,XENOPUS laevis ,ION channels ,MISSENSE mutation - Abstract
A search in the GDC Data Portal revealed 304 documented somatic mutations of the KCNJ3 gene in primary tumors (out of 10.202 cases). Most affected tumor types were carcinomas from uterus, skin and lung, while breast cancer exerted the lowest number of somatic mutations. We focused our research on 15 missense mutations within the region between TM1 and TM2, comprising the pore helix and ion selectivity signature. Expression was measured by confocal laser scan microscopy of eGFP tagged GIRK1 subunits, expressed with and without GIRK4 in oocytes of Xenopus laevis. GIRK ion currents were activated via coexpressed m
2 Rs and measured by the Two Electrode Voltage Clamp technique. Magnitude of the total GIRK current, as well as the fraction of current inducible by the agonist, were measured. Ion selectivity was gauged by assessment of the PNa+ /PK+ ratio, calculated by the GIRK current reversal potential in extracellular media at different Na+ and K+ concentrations. None of the tested mutations was able to form functional GIRK1 homooligomeric ion channels. One of the mutations, G145A, which locates directly to the ion selectivity signature, exerted an increased PNa+ /PK+ ratio. Generally, the missense mutations studied can be categorized into three groups: (i) normal/ reduced expression accompanied by reduced/absent function (S132Y, F136L, E139K, G145A, R149Q, R149P, G178D, S185Y, Q186R), (ii) normal/increased expression as well as increased function (E140M, A142T, M184I) and (iii) miniscule expression but increased function relative to expression levels (I151N, G158S). We conclude, that gain of function mutations, identical or similar to categories (ii) and (iii), may potentially be involved in genesis and progression of malignancies in tissues that exert a high rate of occurrence of somatic mutations of KCNJ3. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
10. Creating a Novel Mathematical Model of the Kv10.1 Ion Channel and Controlling Channel Activity with Nanoelectromechanical Systems.
- Author
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Lozanović Šajić, Jasmina, Langthaler, Sonja, and Baumgartner, Christian
- Subjects
ION channels ,NANOELECTROMECHANICAL systems ,VOLTAGE-gated ion channels ,MATHEMATICAL models ,AUTOMATIC control systems ,SYSTEMS theory - Abstract
Featured Application: Nanoelectromechanical systems and nanorobots can be used to treat cancers associated with the Kv10.1 voltage-gated ion channel activity. The Kv10.1 model was developed by applying the control engineering theory. Nanoelectromechanical systems play the role of a PID regulator. The use of nanoelectromechanical systems or nanorobots offers a new concept for sensing and controlling subcellular structures, such as ion channels. We present here a novel method for mathematical modeling of ion channels based on control system theory and system identification. We investigated the use of nanoelectromechanical devices to control the activity of ion channels, particularly the activity of the voltage-gated ion channel Kv10.1, an important channel in cancer development and progression. A mathematical model of the dynamic behavior of the selected ion channel Kv10.1 in the Laplace (s) domain was developed, which is given in the representation of a transfer function. In addition, we addressed the possibilities of controlling ion channel activity by nanoelectromechanical devices and nanorobots and finally presented a control algorithm for the Kv10.1 as a control object. A use case demonstrates the potential of a Kv10.1 controlled nanorobot for cancer treatment at a single-cell level. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. A549 in-silico 1.0: A first computational model to simulate cell cycle dependent ion current modulation in the human lung adenocarcinoma.
- Author
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Langthaler, Sonja, Rienmüller, Theresa, Scheruebel, Susanne, Pelzmann, Brigitte, Shrestha, Niroj, Zorn-Pauly, Klaus, Schreibmayer, Wolfgang, Koff, Andrew, and Baumgartner, Christian
- Subjects
- *
ION channels , *CELL cycle , *MEMBRANE potential , *CAUSES of death , *CELL proliferation , *ADENOCARCINOMA - Abstract
Lung cancer is still a leading cause of death worldwide. In recent years, knowledge has been obtained of the mechanisms modulating ion channel kinetics and thus of cell bioelectric properties, which is promising for oncological biomarkers and targets. The complex interplay of channel expression and its consequences on malignant processes, however, is still insufficiently understood. We here introduce the first approach of an in-silico whole-cell ion current model of a cancer cell, in particular of the A549 human lung adenocarcinoma, including the main functionally expressed ion channels in the plasma membrane as so far known. This hidden Markov-based model represents the electrophysiology behind proliferation of the A549 cell, describing its rhythmic oscillation of the membrane potential able to trigger the transition between cell cycle phases, and it predicts membrane potential changes over the cell cycle provoked by targeted ion channel modulation. This first A549 in-silico cell model opens up a deeper insight and understanding of possible ion channel interactions in tumor development and progression, and is a valuable tool for simulating altered ion channel function in lung cancer electrophysiology. Author summary: Advances in the understanding of functional alterations at genetic, epigenetic or protein expression and the expanding knowledge in mechanisms modulating ion channel kinetics and thus the cells' bioelectric properties have arisen as promising cancer biomarkers and oncological targets. Our hidden Markov-based in-silico cell model represents the electrophysiology behind proliferation of the A549 cell line, explaining the cell's rhythmic oscillation from hyperpolarized to depolarized states of the membrane potential, able to trigger the transition between cell cycle phases. The model enables the prediction of membrane potential changes over the cell cycle provoked by targeted modulation of specific ion channels, leading to cell cycle promotion or interruption. We are encouraged that the availability of this first cancer cell model will provide profound insight into possible roles and interactions of ion channels in tumor development and progression, and may aid in the testing of research hypotheses in lung cancer electrophysiology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
12. A novel network-based approach for discovering dynamic metabolic biomarkers in cardiovascular disease.
- Author
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Baumgartner, Christian, Spath-Blass, Verena, Niederkofler, Verena, Bergmoser, Katharina, Langthaler, Sonja, Lassnig, Alexander, Rienmüller, Theresa, Baumgartner, Daniela, Asnani, Aarti, and Gerszten, Robert E.
- Subjects
CARDIOVASCULAR disease diagnosis ,REPRESENTATIONS of graphs ,CLINICAL medicine ,TIME series analysis ,DATA analysis - Abstract
Metabolic biomarkers may play an important role in the diagnosis, prognostication and assessment of response to pharmacological therapy in complex diseases. The process of discovering new metabolic biomarkers is a non-trivial task which involves a number of bioanalytical processing steps coupled with a computational approach for the search, prioritization and verification of new biomarker candidates. Kinetic analysis provides an additional dimension of complexity in time-series data, allowing for a more precise interpretation of biomarker dynamics in terms of molecular interaction and pathway modulation. A novel network-based computational strategy for the discovery of putative dynamic biomarker candidates is presented, enabling the identification and verification of unexpected metabolic signatures in complex diseases such as myocardial infarction. The novelty of the proposed method lies in combining metabolic time-series data into a superimposed graph representation, highlighting the strength of the underlying kinetic interaction of preselected analytes. Using this approach, we were able to confirm known metabolic signatures and also identify new candidates such as carnosine and glycocholic acid, and pathways that have been previously associated with cardiovascular or related diseases. This computational strategy may serve as a complementary tool for the discovery of dynamic metabolic or proteomic biomarkers in the field of clinical medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
13. P015. Describing cardiac ICU patients' fluid transfer characteristics using system analysis: a proof of concept.
- Author
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Bergmoser, Katharina, Pflanzl-Knizacek, Lucas, Langthaler, Sonja, and Baumgartner, Christian
- Published
- 2019
14. Ion Channel Modeling beyond State of the Art: A Comparison with a System Theory-Based Model of the Shaker-Related Voltage-Gated Potassium Channel Kv1.1.
- Author
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Langthaler, Sonja, Lozanović Šajić, Jasmina, Rienmüller, Theresa, Weinberg, Seth H., and Baumgartner, Christian
- Subjects
- *
ION channels , *VOLTAGE-gated ion channels , *POTASSIUM channels , *HIDDEN Markov models , *BIOLOGICAL systems , *TRANSFER functions - Abstract
The mathematical modeling of ion channel kinetics is an important tool for studying the electrophysiological mechanisms of the nerves, heart, or cancer, from a single cell to an organ. Common approaches use either a Hodgkin–Huxley (HH) or a hidden Markov model (HMM) description, depending on the level of detail of the functionality and structural changes of the underlying channel gating, and taking into account the computational effort for model simulations. Here, we introduce for the first time a novel system theory-based approach for ion channel modeling based on the concept of transfer function characterization, without a priori knowledge of the biological system, using patch clamp measurements. Using the shaker-related voltage-gated potassium channel Kv1.1 (KCNA1) as an example, we compare the established approaches, HH and HMM, with the system theory-based concept in terms of model accuracy, computational effort, the degree of electrophysiological interpretability, and methodological limitations. This highly data-driven modeling concept offers a new opportunity for the phenomenological kinetic modeling of ion channels, exhibiting exceptional accuracy and computational efficiency compared to the conventional methods. The method has a high potential to further improve the quality and computational performance of complex cell and organ model simulations, and could provide a valuable new tool in the field of next-generation in silico electrophysiology. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
15. Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca 2+ Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices.
- Author
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Rienmuller T, Shrestha N, Polz M, Stoppacher S, Ziesel D, Migliaccio L, Pelzmann B, Lang P, Zorn-Pauly K, Langthaler S, Opancar A, Baumgartner C, Ucal M, Schindl R, Derek V, and Scheruebel S
- Subjects
- Animals, Guinea Pigs, Patch-Clamp Techniques, Models, Cardiovascular, Action Potentials physiology, Action Potentials radiation effects, Light, Myocytes, Cardiac physiology, Calcium Channels, L-Type metabolism, Computer Simulation
- Abstract
Objective: This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (I
Ca,L ) in Guinea pig ventricular cardiomyocytes., Methods: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated ICa,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes., Results: Light pulses activated ICa,L , with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered ICa,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation., Conclusion: OEPC-mediated activation of ICa,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of ICa,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices., Significance: Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.- Published
- 2024
- Full Text
- View/download PDF
16. Consequences of somatic mutations of GIRK1 detected in primary malign tumors on expression and function of G-protein activated, inwardly rectifying, K + channels.
- Author
-
Pelzmann B, Hatab A, Scheruebel S, Langthaler S, Rienmueller T, Sokolowski A, Gorischek A, Platzer D, Zorn-Pauly K, Jahn SW, Bauernhofer T, and Schreibmayer W
- Abstract
A search in the GDC Data Portal revealed 304 documented somatic mutations of the KCNJ3 gene in primary tumors (out of 10.202 cases). Most affected tumor types were carcinomas from uterus, skin and lung, while breast cancer exerted the lowest number of somatic mutations. We focused our research on 15 missense mutations within the region between TM1 and TM2, comprising the pore helix and ion selectivity signature. Expression was measured by confocal laser scan microscopy of eGFP tagged GIRK1 subunits, expressed with and without GIRK4 in oocytes of Xenopus laevis . GIRK ion currents were activated via coexpressed m
2 Rs and measured by the Two Electrode Voltage Clamp technique. Magnitude of the total GIRK current, as well as the fraction of current inducible by the agonist, were measured. Ion selectivity was gauged by assessment of the PNa+ /PK+ ratio, calculated by the GIRK current reversal potential in extracellular media at different Na+ and K+ concentrations. None of the tested mutations was able to form functional GIRK1 homooligomeric ion channels. One of the mutations, G145A, which locates directly to the ion selectivity signature, exerted an increased PNa+ /PK+ ratio. Generally, the missense mutations studied can be categorized into three groups: (i) normal/reduced expression accompanied by reduced/absent function (S132Y, F136L, E139K, G145A, R149Q, R149P, G178D, S185Y, Q186R), (ii) normal/increased expression as well as increased function (E140M, A142T, M184I) and (iii) miniscule expression but increased function relative to expression levels (I151N, G158S). We conclude, that gain of function mutations, identical or similar to categories (ii) and (iii), may potentially be involved in genesis and progression of malignancies in tissues that exert a high rate of occurrence of somatic mutations of KCNJ3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pelzmann, Hatab, Scheruebel, Langthaler, Rienmueller, Sokolowski, Gorischek, Platzer, Zorn-Pauly, Jahn, Bauernhofer and Schreibmayer.)- Published
- 2022
- Full Text
- View/download PDF
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