Ion channels and disease

2020 ◽  
pp. 246-255
Author(s):  
Frances Ashcroft ◽  
Paolo Tammaro
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Single Channel ◽  
Cell Types ◽  
Channel Structure ◽  
Channel Proteins ◽  
Channel Function ◽  
Ion Channel Proteins ◽  
Single Channel Currents ◽  
Channel Currents

Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They are found in both surface and intracellular membranes and play essential roles in the physiology of all cell types. An ever-increasing number of human diseases are now known to be caused by defects in ion channel function. To understand how ion channel defects give rise to disease, it is helpful to understand how the ion channel proteins work. This chapter therefore considers what is known of ion channel structure, explains the properties of the single ion channel, and shows how single-channel currents give rise to action potentials and synaptic potentials.

scholarly journals Unsupervised idealization of ion channel recordings by Minimum Description Length: Application to human PIEZO1-channels

2017 ◽  
Author(s):  
Radhakrishnan Gnanasambandam ◽  
Morten Schak Nielsen ◽  
Christopher Nicolai ◽  
Frederick Sachs ◽  
Johannes Pauli Hofgaard ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Markov Models ◽  
Single Channel ◽  
Minimum Description Length ◽  
Simulated Data ◽  
Multiple Channels ◽  
Electrophysiological Recordings ◽  
Single Channel Currents ◽  
Channel Currents

AbstractResearchers can investigate the mechanistic and molecular basis of many physiological phenomena in cells by analyzing the fundamental properties of single ion channels. These analyses entail recording single channel currents and measuring current amplitudes and transition rates between conductance states. Since most electrophysiological recordings contain noise, the data analysis can proceed by idealizing the recordings to isolate the true currents from the noise. This de-noising can be accomplished with threshold crossing algorithms and Hidden Markov Models, but such procedures generally depend on inputs and supervision by the user, thus requiring some prior knowledge of underlying processes. Channels with unknown gating and/or functional sub-states and the presence in the recording of currents from uncorrelated background channels present substantial challenges to unsupervised analyses.Here we describe and characterize an idealization algorithm based on Rissanen’s Minimum Description Length (MDL) Principle. This method uses minimal assumptions and idealizes ion channel recordings without requiring a detailed user input or a priori assumptions about channel conductance and kinetics.. Furthermore, we demonstrate that correlation analysis of conductance steps can resolve properties of single ion channels in recordings contaminated by signals from multiple channels. We first validated our methods on simulated data defined with a range of different signal-to-noise levels, and then showed that our algorithm can recover channel currents and their substates from recordings with multiple channels, even under conditions of high noise. We then tested the MDL algorithm on real experimental data from human PIEZO1 channels and found that our method revealed the presence of substates with alternate conductances.

On the stochastic properties of single ion channels

1981 ◽  
Vol 211 (1183) ◽  
pp. 205-235 ◽  
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
The State ◽  
Agonist Action ◽  
Agonist Concentration ◽  
Relaxation Experiments ◽  
Flow Through ◽  
Single Channel Currents ◽  
Stochastic Properties ◽  
Channel Currents

It is desirable to be able to predict, from a specified mechanism, the appearance of currents that flow through single ion channels ( a ) to enable interpretation of experiments in which single channel currents are observed, and ( b ) to allow physical meaning to be attached to the results observed in kinetic (noise and relaxation) experiments in which the aggregate of many single channel currents is observed. With this object, distributions (and their means) are derived for the length of the sojourn in any specified subset of states (e. g. all shut states). In general these are found to depend not only on the state in which the sojourn starts, but also on the state that immediately follows the sojourn. The methods described allow derivation of the distribution of, for example, ( a ) the number of openings, and total length of the burst of openings, that may occur during a single occupancy, and ( b ) the apparent gap between such bursts. The methods are illustrated by their application to two simple theories of agonist action. The Castillo-Katz (non-cooperative) mechanism predicts, for example, that the number of openings per occupancy, and the apparent burst length, are independent of agonist concentration whereas a simple cooperative mechanism predicts that both will increase with agonist concentration.

WHAT CAUSES ION CHANNEL PROTEINS TO FLUCTUATE OPEN AND CLOSED?

1996 ◽  
Vol 07 (04) ◽  
pp. 321-331 ◽  
Author(s):  
LARRY S. LIEBOVITCH ◽  
ANGELO T. TODOROV
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Patch Clamp Technique ◽  
Sodium Potassium ◽  
Random Event ◽  
Channel Protein ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Open States

Ion channels in the cell membrane spontaneously switch from states that are closed to the flow of ions such as sodium, potassium, and chloride to states that are open to the flow of these ions. The durations of times that an individual ion channel protein spends in the closed and open states can be measured by the patch clamp technique. We explore two basic issues about the molecular properties of ion channels: 1) If the switching between the closed and open state is an inherently random event, what does the patch clamp data tell us about the structure or motions in the ion channel protein? 2) Is this switching random?

scholarly journals The nature and origin of spontaneous noise in G protein-gated ion channels.

1991 ◽  
Vol 97 (6) ◽  
pp. 1279-1293 ◽  
Author(s):  
K Okabe ◽  
A Yatani ◽  
A M Brown
Keyword(s):  
Ion Channels ◽  
G Protein ◽  
Single Channel ◽  
Coupled Systems ◽  
Dependent Manner ◽  
Protein Receptor ◽  
Spontaneous Noise ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Inside Out

Arrival of agonist is generally thought to initiate the signal transduction process in G protein-receptor coupled systems. However, the muscarinic atrial K+ (K+[ACh]) channel opens spontaneously in the absence of applied agonist, giving a noisy appearance to the current records. We investigated the nature and origin of the noise by measuring single channel currents in cell-attached or excised, inside-out membrane patches. Guanosine triphosphate (GTP) produced identical single channel currents in a concentration- and Mg(2+)-dependent manner in the presence or absence of carbachol, but the requirements for GTP were greater in the absence of agonist. Hence the agonist-independent currents appeared to be produced by an endogenous G protein, Gk. This prediction was confirmed when an affinity-purified, sequence-specific Gi-3 alpha antibody or pertussis toxin (PTX) blocked the agonist-independent currents. Candidate endogenous agonists were ruled out by the lack of effect of their corresponding antagonists. Thus agonist-independent currents had the same nature as agonist-dependent K+[ACh] currents and seemed to originate in the same way. We have developed a hypothesis in which agonist-free, empty receptors prime Gk with GTP and Gk activates atrial K+ [ACh] channels producing basal currents or noise. Agonist-independent activation by G proteins of effectors including ion channels appears to be a common occurrence.

scholarly journals On hysteresis of ion channels

2020 ◽  
Vol 15 ◽  
pp. 26
Author(s):  
Can E. Korman ◽  
Isaak D. Mayergoyz
Keyword(s):  
Ion Channel ◽  
Stochastic Processes ◽  
Action Potentials ◽  
Single Channel ◽  
Hysteresis Loops ◽  
Exit Problem ◽  
Stochastic Nature ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Sodium And Potassium

Ion channel proteins have many conformational (metastable) states and, for this reason, they exhibit hysteresis. This fact is responsible for the non-Markovian stochastic nature of single ion channel recordings. It is suggested in the paper that the stochastic single channel recordings can be modeled as the random outputs of rectangular hysteresis loops driven by stochastic processes. The latter problem can be mathematically treated as an exit problem for stochastic processes or by using the theory of stochastic processes on graphs. It is also demonstrated in the paper that the collective action of sodium and potassium channels responsible for the generation and propagation of action potentials exhibit hysteresis. This demonstration is accomplished by using the inverse problem approach to the nonlinear Hodgkin-Huxley diffusion equation.

scholarly journals Precise control of ion channel and gap junction expression is required for patterning of the regenerating axolotl limb

2020 ◽  
Vol 64 (10-11-12) ◽  
pp. 485-494
Author(s):  
Konstantinos Sousounis ◽  
Burcu Erdogan ◽  
Michael Levin ◽  
Jessica L. Whited
Keyword(s):  
Ion Channels ◽  
Gap Junctions ◽  
Ion Channel ◽  
Gap Junction ◽  
Regulation Of Gene Expression ◽  
Transcriptional Networks ◽  
Channel Proteins ◽  
Junction Protein ◽  
Ion Channel Proteins ◽  
Voltage Gradients

Axolotls and other salamanders have the capacity to regenerate lost tissue after an amputation or injury. Growth and morphogenesis are coordinated within cell groups in many contexts by the interplay of transcriptional networks and biophysical properties such as ion flows and voltage gradients. It is not, however, known whether regulators of a cell’s ionic state are involved in limb patterning at later stages of regeneration. Here we manipulated expression and activities of ion channels and gap junctions in vivo, in axolotl limb blastema cells. Limb amputations followed by retroviral infections were performed to drive expression of a human gap junction protein Connexin 26 (Cx26), potassium (Kir2.1-Y242F and Kv1.5) and sodium (NeoNav1.5) ion channel proteins along with EGFP control. Skeletal preparation revealed that overexpressing Cx26 caused syndactyly, while overexpression of ion channel proteins resulted in digit loss and structural abnormalities compared to EGFP expressing control limbs. Additionally, we showed that exposing limbs to the gap junction inhibitor lindane during the regeneration process caused digit loss. Our data reveal that manipulating native ion channel and gap junction function in blastema cells results in patterning defects involving the number and structure of the regenerated digits. Gap junctions and ion channels have been shown to mediate ion flows that control the endogenous voltage gradients which are tightly associated with the regulation of gene expression, cell cycle progression, migration, and other cellular behaviors. Therefore, we postulate that mis-expression of these channels may have disturbed this regulation causing uncoordinated cell behavior which results in morphological defects.

Regulation of ion channel structure and function by reactive oxygen-nitrogen species

2003 ◽  
Vol 285 (6) ◽  
pp. L1184-L1189 ◽  
Author(s):  
Sadis Matalon ◽  
Karin M. Hardiman ◽  
Lucky Jain ◽  
Douglas C. Eaton ◽  
Michael Kotlikoff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ion Channels ◽  
Ion Channel ◽  
Posttranslational Modifications ◽  
Regulation Of Gene Expression ◽  
Reactive Oxygen ◽  
Cellular Level ◽  
Channel Structure ◽  
Nitrogen Species ◽  
Channel Proteins

Ion channels subserve diverse cellular functions. Reactive oxygen and nitrogen species modulate ion channel function by a number of mechanisms including 1) transcriptional regulation of gene expression, 2) posttranslational modifications of channel proteins, i.e. nitrosylation, nitration, and oxidation of key amino acid residues, 3) by altering the gain in other signaling pathways that may in turn lead to changes in channel activity or channel gene expression, and 4) by modulating trafficking or turnover of channel proteins, as typified by oxygen radical activation of NF-kB, with subsequent changes in proteasomal degradation of channel degradation. Regardless of the mechanism, as was discussed in a symposium at the 2003 Experimental Biology Meeting in San Diego, CA, changes in the cellular level of reactive oxygen and nitrogen species can have profound effects on the activity of ion channels and cellular function.

New Roles for Old Holes: Ion Channel Function in Aquaporin-1

Physiology ◽  
2002 ◽  
Vol 17 (2) ◽  
pp. 68-72 ◽  
Author(s):  
Andrea J. Yool ◽  
Alan M. Weinstein
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Functional Properties ◽  
Major Intrinsic Protein ◽  
Aquaporin 1 ◽  
Intrinsic Protein ◽  
Channel Proteins ◽  
Channel Function ◽  
Transmembrane Channel ◽  
Structural And Functional Properties

Mammalian aquaporins are part of the diverse major intrinsic protein family of water and solute channels. Intriguing links exist in structural and functional properties between aquaporins and ion channels. A novel role for aquaporin-1 as a gated ion channel reshapes our current views of this ancient family of transmembrane channel proteins.

scholarly journals Parallel Recordings of Transmembrane hERG Channel Currents Based on Solvent-Free Lipid Bilayer Microarray

Micromachines ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 98
Author(s):  
Ryusuke Miyata ◽  
Daisuke Tadaki ◽  
Daichi Yamaura ◽  
Shun Araki ◽  
Madoka Sato ◽  
...  
Keyword(s):  
Ion Channel ◽  
Lipid Membranes ◽  
Solvent Free ◽  
Bilayer Lipid Membranes ◽  
Related Gene ◽  
Recording Site ◽  
Channel Proteins ◽  
Free Lipid ◽  
Ion Channel Proteins ◽  
Channel Currents

The reconstitution of ion-channel proteins in artificially formed bilayer lipid membranes (BLMs) forms a well-defined system for the functional analysis of ion channels and screening of the effects of drugs that act on these proteins. To improve the efficiency of the BLM reconstitution system, we report on a microarray of stable solvent-free BLMs formed in microfabricated silicon (Si) chips, where micro-apertures with well-defined nano- and micro-tapered edges were fabricated. Sixteen micro-wells were manufactured in a chamber made of Teflon®, and the Si chips were individually embedded in the respective wells as a recording site. Typically, 11 to 16 BLMs were simultaneously formed with an average BLM number of 13.1, which corresponded to a formation probability of 82%. Parallel recordings of ion-channel activities from multiple BLMs were successfully demonstrated using the human ether-a-go-go-related gene (hERG) potassium channel, of which the relation to arrhythmic side effects following drug treatment is well recognized.

A vesicle preparation for resolving single-channel currents in tegument of male Schistosoma mansoni

Parasitology ◽  
1997 ◽  
Vol 115 (2) ◽  
pp. 183-192 ◽  
Author(s):  
A. P. ROBERTSON ◽  
R. J. MARTIN ◽  
J. R. KUSEL
Keyword(s):  
Electron Microscopy ◽  
Ion Channel ◽  
Schistosoma Mansoni ◽  
Adult Male ◽  
Single Channel ◽  
Patch Clamp Technique ◽  
Fluorescence Studies ◽  
Vesicle Preparation ◽  
Single Channel Currents ◽  
Channel Currents

A tegumental vesicle preparation from adult male Schistosoma mansoni was developed that allows the resolution of single ion-channel currents. Adult male schistosomes were exposed to a low pH (3·75) medium for a period of approximately 30 min at 37°C. During this period smooth vesicles formed from the tegument. Fluorescence microscopy following staining of the tegument with the dye, 5-N-[octadecanoyl]aminofluorescein (AF-18), transmission electron microscopy and scanning electron microscopy revealed that the vesicles were produced from the outer tegumental membrane. The fluorescence studies showed the presence of the double bilayer structure of the outer membrane in >41% of the vesicles. These studies suggested that the preparation is suitable for single-channel recording with the patch-clamp technique. Cell-attached and isolated inside-out patch recordings of ion-channel activity were obtained with giga-ohm resistance seals. Different types of ion-channel were recorded from tegumental vesicles from male schistosomes, illustrating the potential of the technique. The channels observed included: a non-selective cation channel (360 pS); a K+ channel (with a conductance of 115 pS in high bath-K conditions); and a Cl− selective channel (20 pS). The currents of these ion-channels may cross the double bilayer of the outer tegumental membrane.

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