scholarly journals Panama: A tool for ion channel biophysics simulation

2018 ◽  
Author(s):  
Anuj Guruacharya
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Calcium Channels ◽  
Ion Channel ◽  
Chloride Channels ◽  
High Threshold ◽  
Spreadsheet Program ◽  
Online Tool ◽  
Voltage Gated ◽  
Web App

I have created an online tool and an R library that simulates biophysics of voltage-gated ion channels. It is made publicly available as an R library called Panama at github.com/anuj2054/panama and as a web app at neuronsimulator.com. A need for such a tool was observed after surveying available software packages. I found that the available packages are either not robust enough to simulate multiple ion channels, too complicated, usable only as desktop software, not optimized for mobile devices, not interactive, lacking intuitive graphical controls, or not appropriate for undergraduate education. My app simulates the physiology of 11 different channels - voltage-gated sodium, potassium, and chloride channels; channels causing A-current, M-current, and After-HyperPolarization (AHP) current; calcium-activated potassium channels; low threshold T type calcium channels and high threshold L type calcium channels; leak sodium and leak potassium channels. It can simulate these channels under both current clamp and voltage clamp conditions. As we change the input values on the app, the output can be instantaneously visualized on the web browser and downloaded as a data table to be further analyzed in a spreadsheet program. The app is a first of its kind, mobile-friendly and touch-screen-friendly online tool that can be used to teach undergraduate neuroscience classes. It can also be used by researchers on their local computers as part of an R library. It has intuitive touch-optimized controls, instantaneous graphical output, and yet is pedagogically robust for education and casual research purposes.Neuroscience education, ion channel biophysics, Hodgkin-Huxley simulation, web app for neuroscience

scholarly journals Consensus channelome of dinoflagellates revealed by transcriptomic analysis sheds light on their physiology

ALGAE ◽  
2021 ◽  
Vol 36 (4) ◽  
pp. 315-326
Author(s):  
Ilya Pozdnyakov ◽  
Olga Matantseva ◽  
Sergei Skarlato
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Ion Channel ◽  
Chloride Channels ◽  
Cation Channels ◽  
Mechanosensitive Channels ◽  
Anion Channels ◽  
Voltage Gated ◽  
Calcium Activated Potassium Channels ◽  
Pore Domain

Ion channels are membrane protein complexes mediating passive ion flux across the cell membranes. Every organism has a certain set of ion channels that define its physiology. Dinoflagellates are ecologically important microorganisms characterized by effective physiological adaptability, which backs up their massive proliferations that often result in harmful blooms (red tides). In this study, we used a bioinformatics approach to identify homologs of known ion channels that belong to 36 ion channel families. We demonstrated that the versatility of the dinoflagellate physiology is underpinned by a high diversity of ion channels including homologs of animal and plant proteins, as well as channels unique to protists. The analysis of 27 transcriptomes allowed reconstructing a consensus ion channel repertoire (channelome) of dinoflagellates including the members of 31 ion channel families: inwardly-rectifying potassium channels, two-pore domain potassium channels, voltage-gated potassium channels (Kv), tandem Kv, cyclic nucleotide-binding domain-containing channels (CNBD), tandem CNBD, eukaryotic ionotropic glutamate receptors, large-conductance calcium-activated potassium channels, intermediate/small-conductance calcium-activated potassium channels, eukaryotic single-domain voltage-gated cation channels, transient receptor potential channels, two-pore domain calcium channels, four-domain voltage-gated cation channels, cation and anion Cys-loop receptors, small-conductivity mechanosensitive channels, large-conductivity mechanosensitive channels, voltage-gated proton channels, inositole-1,4,5- trisphosphate receptors, slow anion channels, aluminum-activated malate transporters and quick anion channels, mitochondrial calcium uniporters, voltage-dependent anion channels, vesicular chloride channels, ionotropic purinergic receptors, animal volage-insensitive cation channels, channelrhodopsins, bestrophins, voltage-gated chloride channels H+/Cl- exchangers, plant calcium-permeable mechanosensitive channels, and trimeric intracellular cation channels. Overall, dinoflagellates represent cells able to respond to physical and chemical stimuli utilizing a wide range of Gprotein coupled receptors- and Ca2+-dependent signaling pathways. The applied approach not only shed light on the ion channel set in dinoflagellates, but also provided the information on possible molecular mechanisms underlying vital cellular processes dependent on the ion transport.

Neuromodulation-dependent regulation of coordinated patterns of gene expression in motor neurons of the stomatogastric ganglion

2012 ◽  
Author(s):  
◽  
Simone Temporal
Keyword(s):  
Gene Expression ◽  
Ion Channels ◽  
Potassium Channels ◽  
Calcium Channels ◽  
Ion Channel ◽  
Mrna Expression ◽  
Stomatogastric Ganglion ◽  
Muscarinic Agonist ◽  
Burst Frequency ◽  
Network Function

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The pyloric network of the crustacean stomatogastric ganglion (STG) is a central pattern generator that requires descending modulation for normal ongoing rhythmic activity. However, the pyloric rhythm is capable of functional recovery after removal of descending inputs. We used the STG to determine whether or not correlated mRNA ion channels are dependent on neuromodulation. Our hypothesis is that relationships between ion channels are dependent on neuromodulation, not activity. To investigate this, we first measured mRNA expression levels of three calcium channels (Ca1A, Ca1D and T-type-related channel) and two potassium channels (shal and shab), of PD cells to investigate how channel transcription may be modified to influence recovery of burst activity. We collected single PD neurons from both recovered and time-matched control preparations and quantified channel transcript levels with quantitative real-time RT-PCR. There was widespread correlation between all three calcium channels and the two potassium channels in PD cells from intact networks. Specifically, the strongest relationships were between all three calcium channels and the shal channel, which carries an A-type transient potassium current (p[less-than]0.005; R2[greater-than]0.5). Furthermore, our results show that following recovery, there are no significant changes in overall mRNA abundance across all channel types. However, there was a striking lack of any correlation between measured channel types in PD cells following recovery. These results indicate that recovered, decentralized networks do not regain rhythmicity simply by increasing or decreasing mRNA expression for a given channel or channels. In order to determine whether ion channel correlations are dependent on neuromodulation or activity, we decoupled neuromodulatory and activity inputs. We found that preparations with neuromodulatory inputs maintained relationships between mRNA channels while activity input alone did not. Further, addition of pilocarpine, the muscarinic agonist and modulator, to decentralized preparations maintained the same correlations as those found in preparations that only had neuromodulatory input. To determine whether loss of correlations affected network function, we compared the pyloric burst frequency of the different conditions. We found that the pyloric burst frequency decreased under conditions that lost correlations between ion channels due to the removal of neuromodulation. Together, these results indicate that neuromodulation maintains ion channel correlations, which are important to proper network function. They also suggest a possible novel role of neuromodulation in the regulation of gene expression.

Channelopathies: Their Contribution to Our Knowledge About Voltage-Gated Ion Channels

Physiology ◽  
1997 ◽  
Vol 12 (3) ◽  
pp. 105-112
Author(s):  
F Lehmann-Horn ◽  
R Rudel
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Ion Channel ◽  
Chloride Channels ◽  
Gene Products ◽  
Sodium Potassium ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Genes Encoding ◽  
Voltage Gated Ion Channels

Since 1990, many mutations in genes encoding voltage-dependent sodium, potassium, calcium, and chloride channels have been discovered to cause disorders of heart, skeletal muscle, brain, or kidney. Study of the defective gene products has furthered our knowledge not only of pathology but also of ion-channel function.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

Ion Channel Permeation and Selectivity

2019 ◽  
Author(s):  
Juan J. Nogueira ◽  
Ben Corry
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Ionic Currents ◽  
Biological Processes ◽  
Ion Permeation ◽  
Voltage Gated ◽  
Physical Mechanisms ◽  
Theoretical Approaches ◽  
Mechanistic Insight

Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.

Voltage-Gated Ion Channels and Hereditary Disease

1999 ◽  
Vol 79 (4) ◽  
pp. 1317-1372 ◽  
Author(s):  
Frank Lehmann-Horn ◽  
Karin Jurkat-Rott
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Recombinant Dna ◽  
Hereditary Disease ◽  
Hereditary Diseases ◽  
Technological Advancement ◽  
Myotonia Congenita ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.

scholarly journals Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity

2019 ◽  
Author(s):  
Juhwan Lee ◽  
Mooseok Kang ◽  
Sangyeol Kim ◽  
Iksoo Chang
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Potassium Ion ◽  
Low Permeability ◽  
Voltage Gated ◽  
Kv Channels ◽  
Proton Concentration ◽  
Electrical Voltage ◽  
Gating Mechanism ◽  
Ph Dependent

AbstractUnderstanding the gating mechanism of ion channel proteins is key to understanding the regulation of cell signaling through these channels. Channel opening and closing are regulated by diverse environmental factors that include temperature, electrical voltage across the channel, and proton concentration. Low permeability in voltage-gated potassium ion channels (Kv) is intimately correlated with the prolonged action potential duration observed in many acidosis diseases. The Kv channels consist of voltage-sensing domains (S1–S4 helices) and central pore domains (S5–S6 helices) that include a selectivity filter and water-filled cavity. The voltage-sensing domain is responsible for the voltage-gating of Kv channels. While the low permeability of Kv channels to potassium ion is highly correlated with the cellular proton concentration, it is unclear how an intracellular acidic condition drives their closure, which may indicate an additional pH-dependent gating mechanism of the Kv family. Here, we show that two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch. In addition, we present a structural and molecular concept of the pH-dependent gating of Kv1.2 in atomic detail, showing that the protonation of E327 and H418 disrupts the electrostatic balance around the S6 helices, which leads to a straightening transition in the shape of their axes and causes dewetting of the water-filled cavity and closure of the channel. Our work offers a conceptual advancement to the regulation of the pH-dependent gating of various voltage-gated ion channels and their related biological functions.Author SummaryThe acid sensing ion channels are a biological machinery for maintaining the cell functional under the acidic or basic cellular environment. Understanding the pH-dependent gating mechanism of such channels provides the structural insight to design the molecular strategy in regulating the acidosis. Here, we studied the voltage-gated potassium ion channel Kv1.2 which senses not only the electrical voltage across the channels but also the cellular acidity. We uncovered that two key residues E327 and H418 in the pore domain of Kv1.2 channel play a role as pH-switch in that their protonation control the gating of the pore in Kv1.2 channel. It offered a molecular insight how the acidity reduces the ion permeability in voltage-gated potassium channels.

scholarly journals Approaches for unveiling the kinetic mechanisms of voltage gated ion channels in neurons

2019 ◽  
Author(s):  
◽  
Marco Antonio Navarro
Keyword(s):  
Experimental Data ◽  
Ion Channels ◽  
Ion Channel ◽  
Rate Constants ◽  
Markov Models ◽  
Neuronal Firing ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Parameter Constraints ◽  
Gated Ion Channels

Ionic currents drive cellular function within all living cells to perform highly specific tasks. For excitable cells, such as muscle and neurons, voltage-gated ion channels have finely tuned kinetics that allow the transduction of Action potentials to other cells. Voltage-gated ion channels are molecular machines that open and close depending on electrical potential. Neuronal firing rates are largely determined by the overall availability of voltage-gated Na+ and K+ currents.This work describes new approaches for collecting and analyzing experimental data that can be used to streamline experiments. Ion channels are composed of multimeric complexes regulated by intracellular factors producing complex kinetics. The stochastic behavior of thousands of individual ion hannels coordinates to produce cellular activity. To describe their activity and test hypotheses about the channel, experimenters often fit Markov models to a set of experimental data. Markov models are defined by a set of states, whose transitions described by rate constants. To improve the modeling process, we have developed computational approaches to introduce kinetic constraints that reduces the parameter search space. This work describes the implementation and mathematical transformations required to describe linear and non-linear parameter constraints that govern rate constants. Not all ion channel behaviors can easily be described by rate constants. Therefore, we developed and implemented a penalty-based mechanism that can be used to guide the optimization engine to produce a model with a desired behavior, such as single-channel open probability and use dependent effects. To streamline data collection for experiments in brain slice preparations, we developed a 3D virtual software environment that incorporates data from micro-positioning motors and scientific cameras in real-time. This environment provides positional feedback to the investigator and allows for the creation of data maps including both images and electrical recordings. We have also produced semi-automatic targeting procedures that simplifies the overall experimental experience. Experimentally, this work also examines how the kinetic mechanism of voltage gated Na channels regulates the neuronal firing of brainstem respiratory neurons. These raphe neurons are intrinsic pacemakers that do not rely on synaptic connections to elicit activity. I explored how intracellular calcium regulates the kinetics of TTX-sensitive Na+ currents using whole-cell patch clamp electrophysiology. Established with intracellular Ca2+ buffers, high [Ca2+] levels greater than ~7 [micro]M did not change the voltage dependence of steady-state activation and inactivation, but slightly slowed inactivation time course. However, the recovery from inactivation and use dependence inactivation is slowed by high intracellular [Ca2+]. Overall, these approaches described in this work have improved data acquisition and data analysis to create better ion channel models and enhance the electrophysiology experience.

Speed and Noise of Neural Membranes: Ion Channel Limitations to Visual Information Transmission

Perception ◽  
1997 ◽  
Vol 26 (1_suppl) ◽  
pp. 38-38
Author(s):  
M Weckström
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Cell Membrane ◽  
Ion Channel ◽  
Visual Information ◽  
Electrical Response ◽  
Channel Noise ◽  
Maximum Speed ◽  
Voltage Response ◽  
Neural Noise

In dim light, photoreceptor cells and subsequent neural elements typically show high absolute sensitivity, implying that both phototransduction and synaptic transmission work at a high gain and even a single photon may produce a large electrical response. However, when there is more light, rapid adaptation at several levels of signal processing ensures that the information channel is not congested, but optimally filled with relevant voltage responses. All this is achieved by carefully tuned mechanisms that include several types of ion channels in the cell membrane. These ion-channel mechanisms have been thoroughly investigated in a few species of invertebrates and vertebrates, and some general principles are being revealed. The membrane capacitance and the resistance of the cell together define the time constant of the membrane, thus the maximum speed for building up a voltage response to light. Both in vertebrate cones and in insect microvillar photoreceptors, phototransduction takes place in an enlarged part of the cell membrane, which implies a large capacitance. This can be counteracted by making the membrane more leaky by opening more ion channels. In insect photoreceptors several types of potassium channels have been identified that perform exactly this kind of function. The types of channels vary according to the required speed of phototransduction, ie depending on the life style of the animal. In diurnal dipteran insects the potassium channels are typically of the slowly inactivating type. This channel type regulates the cell impedance according to the depolarisation caused by light stimulation. In insects active in dim environments, the potassium channels found have been predominantly rapidly inactivating. The function of this type of channels is currently under debate. In vertebrate photoreceptors several potassium channel types, including channels sensitive to intracellular calcium and pH, are expressed in the inner segments and modulate photoresponses. Opening and closing of the potassium channels also generates neural noise and thus degrades the signal-to-noise ratio (SNR). However, if the gain of phototransduction is high enough, the dominant noise comes from photon fluctuations, or from the biochemical transduction machinery, or—in some situations—from spontaneous photon-like events. Channel noise is then insignificant by comparison. Thus the optimisation of the SNR is a trade-off between bandwidth (ie speed) and amplification of the signal, and here the voltage-gated potassium channels are of prime importance.

Sign in / Sign up

Export Citation Format

Share Document