scholarly journals Hysteretic Behavior in Voltage-Gated Channels

2020 ◽  
Vol 11 ◽  
Author(s):  
Carlos A. Villalba-Galea ◽  
Alvin T. Chiem
Keyword(s):  
Ion Channels ◽  
Hysteretic Behavior ◽  
Channel Activity ◽  
Apparent Contradiction ◽  
Molecular Systems ◽  
Voltage Gated ◽  
Hysteretic Systems ◽  
Gated Channel ◽  
Voltage Gated Channels ◽  
Voltage Gated Ion Channels

An ever-growing body of evidence has shown that voltage-gated ion channels are likely molecular systems that display hysteresis in their activity. This phenomenon manifests in the form of dynamic changes in both their voltage dependence of activity and their deactivation kinetics. The goal of this review is to provide a clear definition of hysteresis in terms of the behavior of voltage-gated channels. This review will discuss the basic behavior of voltage-gated channel activity and how they make these proteins into systems displaying hysteresis. It will also provide a perspective on putative mechanisms underlying hysteresis and explain its potential physiological relevance. It is uncertain whether all channels display hysteresis in their behavior. However, the suggested notion that ion channels are hysteretic systems directly collides with the well-accepted notion that ion channel activity is stochastic. This is because hysteretic systems are regarded to have “memory” of previous events while stochastic processes are regarded as “memoryless.” This review will address this apparent contradiction, providing arguments for the existence of processes that can be simultaneously hysteretic and stochastic.

Prediction of Ion Channels and their Types from Protein Sequences: Comprehensive Review and Comparative Assessment

2019 ◽  
Vol 20 (5) ◽  
pp. 579-592 ◽  
Author(s):  
Jianzhao Gao ◽  
Zhen Miao ◽  
Zhaopeng Zhang ◽  
Hong Wei ◽  
Lukasz Kurgan
Keyword(s):  
Ion Channels ◽  
Empirical Analysis ◽  
Protein Sequences ◽  
Voltage Gated ◽  
New Methods ◽  
Predictive Quality ◽  
Label Prediction ◽  
Gated Channel ◽  
Comprehensive Survey ◽  
Voltage Gated Channels

Background: Ion channels are a large and growing protein family. Many of them are associated with diseases, and consequently, they are targets for over 700 drugs. Discovery of new ion channels is facilitated with computational methods that predict ion channels and their types from protein sequences. However, these methods were never comprehensively compared and evaluated. </P><P> Objective: We offer first-of-its-kind comprehensive survey of the sequence-based predictors of ion channels. We describe eight predictors that include five methods that predict ion channels, their types, and four classes of the voltage-gated channels. We also develop and use a new benchmark dataset to perform comparative empirical analysis of the three currently available predictors. </P><P> Results: While several methods that rely on different designs were published, only a few of them are currently available and offer a broad scope of predictions. Support and availability after publication should be required when new methods are considered for publication. Empirical analysis shows strong performance for the prediction of ion channels and modest performance for the prediction of ion channel types and voltage-gated channel classes. We identify a substantial weakness of current methods that cannot accurately predict ion channels that are categorized into multiple classes/types. </P><P> Conclusion: Several predictors of ion channels are available to the end users. They offer practical levels of predictive quality. Methods that rely on a larger and more diverse set of predictive inputs (such as PSIONplus) are more accurate. New tools that address multi-label prediction of ion channels should be developed.

scholarly journals Fluorescence Imaging of Electrically Stimulated Cells

2003 ◽  
Vol 8 (6) ◽  
pp. 660-667 ◽  
Author(s):  
Paul Burnett ◽  
Janet K. Robertson ◽  
Jeffrey M. Palmer ◽  
Richard R. Ryan ◽  
Adrienne E. Dubin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Ion Channel ◽  
High Throughput ◽  
Pharmacological Intervention ◽  
Voltage Gradient ◽  
Channel Activity ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Designing high-throughput screens for voltage-gated ion channels has been a tremendous challenge for the pharmaceutical industry because channel activity is dependent on the transmembrane voltage gradient, a stimulus unlike ligand binding to G-protein-coupled receptors or ligand-gated ion channels. To achieve an acceptable throughput, assays to screen for voltage-gated ion channel modulators that are employed today rely on pharmacological intervention to activate these channels. These interventions can introduce artifacts. Ideally, a high-throughput screen should not compromise physiological relevance. Hence, a more appropriate method would activate voltage-gated ion channels by altering plasma membrane potential directly, via electrical stimulation, while simultaneously recordingthe operation of the channel in populations of cells. The authors present preliminary results obtained from a device that is designed to supply precise and reproducible electrical stimuli to populations of cells. Changes in voltage-gated ion channel activity were monitored using a digital fluorescent microscope. The prototype electric field stimulation (EFS) device provided real-time analysis of cellular responsiveness to physiological and pharmacological stimuli. Voltage stimuli applied to SK-N-SH neuroblastoma cells cultured on the EFS device evoked membrane potential changes that were dependent on activation of voltage-gated sodium channels. Data obtained using digital fluorescence microscopy suggests suitability of this system for HTS.

Voltage-Gated Ion Channels in Nociceptors: Modulation by cGMP

2004 ◽  
Vol 92 (4) ◽  
pp. 2323-2332 ◽  
Author(s):  
L. Liu ◽  
T. Yang ◽  
M. J. Bruno ◽  
O. S. Andersen ◽  
S. A. Simon
Keyword(s):  
Ion Channels ◽  
Delayed Rectifier ◽  
Channel Activity ◽  
Nociceptive Neurons ◽  
Voltage Gated ◽  
Channel Function ◽  
Proinflammatory Mediators ◽  
Whole Cell Patch Clamp ◽  
Voltage Gated Ion Channels ◽  
Ganglion Neurons

In tissue or nerve injury, proinflammatory mediators are released that can modulate a variety of ion channels found in nociceptors. The changes in channel activity, which primarily occurs through changes in intracellular pathways, may lead to the pathological states of hyperalgesia and allodynia. To understand further the regulatory mechanisms underlying the changes in channel activity, we used whole cell patch-clamp recordings from capsaicin-sensitive nociceptive neurons in rat trigeminal ganglion neurons to examine how the cGMP-dependent pathways may regulate ion channel function. Addition of the 8-(4-chlorophenylthio)-3′,5′ (CPT)-cGMP, a membrane permeant modulator of ion channels, decreased the number of evoked action potentials by 36% and inhibited the tetrodotoxin-resistant (TTX-R) sodium currents and IA potassium currents by 37 and 32%, respectively. Delayed rectifier potassium ( IK) currents were unaffected, suggesting that the effects of CPT-cGMP are unlikely to arise from a nonspecific effect on channel activity as a consequence of the adsorption of amphipathic CPT-cGMP molecules to the membrane's bilayer component. This conclusion was reinforced by the lack of changes in gramicidin A channel function in the presence of CTP-cGMP. In summary, the activation of the cGMP-dependent pathways reduces nociceptor excitability, in part, by decreasing the activity of voltage-gated TTX-R sodium channels. This pathway may be a target for efforts to produce selective analgesics.

Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research

2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  
Keyword(s):  
Cancer Research ◽  
Ion Channels ◽  
Voltage Gated ◽  
New Targets ◽  
Anti Cancer ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Expression and Distribution of Voltage Gated Ion Channels in Ferret SA Node

2009 ◽  
Vol 96 (3) ◽  
pp. 261a
Author(s):  
Muugu V. Brahmajothi ◽  
Michael. J. Morales ◽  
Donald L. Campbell ◽  
Charles Steenbergen ◽  
Harold C. Strauss
Keyword(s):  
Ion Channels ◽  
Voltage Gated ◽  
Sa Node ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels
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