scholarly journals 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

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 239
Author(s):  
Sonja Langthaler ◽  
Jasmina Lozanović Šajić ◽  
Theresa Rienmüller ◽  
Seth H. Weinberg ◽  
Christian Baumgartner
Keyword(s):  
System Theory ◽  
Ion Channel ◽  
Potassium Channel ◽  
Structural Changes ◽  
Channel Modeling ◽  
Computational Effort ◽  
Model Simulations ◽  
Voltage Gated ◽  
Computational Performance ◽  
Ion Channel Modeling

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.

Voltage clamp fluorimetry studies of mammalian voltage-gated K+ channel gating

2007 ◽  
Vol 35 (5) ◽  
pp. 1080-1082 ◽  
Author(s):  
T.W. Claydon ◽  
D. Fedida
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Real Time ◽  
Voltage Clamp ◽  
Conformational Changes ◽  
Channel Gating ◽  
K Channel ◽  
Voltage Gated ◽  
Kv Channels ◽  
Health And Disease

VCF (voltage clamp fluorimetry) provides a powerful technique to observe real-time conformational changes that are associated with ion channel gating. The present review highlights the insights such experiments have provided in understanding Kv (voltage-gated potassium) channel gating, with particular emphasis on the study of mammalian Kv1 channels. Further applications of VCF that would contribute to our understanding of the modulation of Kv channels in health and disease are also discussed.

Bayesian Approaches for Mechanistic Ion Channel Modeling

2013 ◽  
pp. 247-272 ◽  
Author(s):  
Ben Calderhead ◽  
Michael Epstein ◽  
Lucia Sivilotti ◽  
Mark Girolami
Keyword(s):  
Ion Channel ◽  
Channel Modeling ◽  
Bayesian Approaches ◽  
Ion Channel Modeling

scholarly journals Oleamide in Ipomoea and Dillenia species and inflammatory activity investigated through ion channel inhibition

2020 ◽  
Vol 21 ◽  
Author(s):  
Unchaleeporn Ameamsri ◽  
Arunrat Chaveerach ◽  
Runglawan Sudmoon ◽  
Tawatchai Tanee ◽  
Steve Peigneur ◽  
...  
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Sodium Channel ◽  
Ex Vivo ◽  
Inflammatory Activity ◽  
Leaf Extracts ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Inhibition ◽  
Anti Inflammatory

Background: Oleamide is an essential substance for human health. So, the plants with high oleamide content are great sources for health care products. Objective: This study is conducted to investigate the quality of oleamide in plants and test the bioactivity in the selected two studied species. Methods: The three Ipomoea and five Dillenia species including Ipomoea alba, Ipomoea aquatica and Ipomoea pes-caprae, and Dillenia indica, Dillenia obovata, Dillenia ovata, Dillenia parviflora and Dillenia pentagyna were investigated for the quantity of oleamide by high-performance liquid chromatography. The biological activity test was conducted on the powder formulation of the chosen plants, Dillenia ovata and Dillenia parviflora at a ratio of 30:70, for anti-inflammatory activity ex vivo on a panel of molecular targets through ion channel inhibition including voltage-gated sodium channel, voltage-gated potassium channel, and the cardiac ion as human ether-a-go-go related gene. Results: The results showed that the leaf extracts of I. aquatica and D. ovata gave the highest and subsequent oleamide quantity following 7.52 and 5.17 mg/g. Out of the Dillenia formulation which contained various compounds, oleamide showed the highest percentages of inhibition at 8.0-20.0%, and 6.2-14.2% in voltage-gated sodium channel, and voltage-gated potassium channel which had slightly lower values than the oleamide standard, and no effect as 0.0% value inhibition in the cardiac ion channel. Conclusion: The Dillenia formulation exhibits anti-inflammatory activity without affecting the heart. Accordingly, the three studied Ipomoea and three studied Dillenia species may be used for the same activity as a single component or formulation with effective solvent for disease treatments.

Molecular basis for the toxin insensitivity of scorpion voltage-gated potassium channel MmKv1

2016 ◽  
Vol 473 (9) ◽  
pp. 1257-1266 ◽  
Author(s):  
Chuangeng Zhang ◽  
Zili Xie ◽  
Xinxin Li ◽  
Jing Chen ◽  
Jing Feng ◽  
...  
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Molecular Basis ◽  
Receptor Level ◽  
Voltage Gated ◽  
Venomous Animals

Our work is the first to uncover the mechanisms by which scorpions resist their own venoms at the ion channel receptor level and enriched our knowledge of the co-evolution of venomous animals and their venoms for hundreds of million years.

scholarly journals Calcium and Potassium Channels in Experimental Subarachnoid Hemorrhage and Transient Global Ischemia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Marcel A. Kamp ◽  
Maxine Dibué ◽  
Toni Schneider ◽  
Hans-Jakob Steiger ◽  
Daniel Hänggi
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Animal Models ◽  
Ion Channel ◽  
Potassium Channel ◽  
Global Ischemia ◽  
Voltage Gated ◽  
Delayed Cerebral Vasospasm ◽  
Channel Expression ◽  
Transient Global Ischemia ◽  
And Function

Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. Furthermore, expression patterns and function of ion channels appear to differ between main and small peripheral vessels, which may be key in understanding mechanisms behind subarachnoid hemorrhage-induced vasospasm. Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed.

scholarly journals Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors

2018 ◽  
Vol 150 (8) ◽  
pp. 1215-1230 ◽  
Author(s):  
Sara I. Liin ◽  
Per-Eric Lund ◽  
Johan E. Larsson ◽  
Johan Brask ◽  
Björn Wallner ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Potassium Channel ◽  
Voltage Sensor ◽  
Pharmaceutical Drugs ◽  
Voltage Gated ◽  
Channel Opening ◽  
Ion Conducting ◽  
Voltage Gated Ion Channels

Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential–generating sodium and calcium channels and open an action potential–dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.

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