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A small fraction of strongly cooperative sodium channels boosts neuronal encoding of high frequencies.

Huang M, Volgushev M, Wolf F - PLoS ONE (2012)

Bottom Line: Models with a small fraction, [Formula: see text], of strongly cooperative channels generate APs with the most rapid onset dynamics.In this regime APs are triggered by simultaneous opening of the cooperative channel fraction and exhibit a pronounced biphasic waveform often observed in cortical neurons.We conclude that presence of a small fraction of strongly coupled sodium channels can explain characteristic features of cortical APs and has a functional impact of enhancing the spike encoding of rapidly varying signals.

View Article: PubMed Central - PubMed

Affiliation: Max-Planck-Institute for Dynamics and Self-Organization, Bernstein Center for Computational Neuroscience, and Faculty of Physics, Georg August University School of Science, Göttingen, Germany.

ABSTRACT
Generation of action potentials (APs) is a crucial step in neuronal information processing. Existing biophysical models for AP generation almost universally assume that individual voltage-gated sodium channels operate statistically independently, and their avalanche-like opening that underlies AP generation is coordinated only through the transmembrane potential. However, biological ion channels of various types can exhibit strongly cooperative gating when clustered. Cooperative gating of sodium channels has been suggested to explain rapid onset dynamics and large threshold variability of APs in cortical neurons. It remains however unknown whether these characteristic properties of cortical APs can be reproduced if only a fraction of channels express cooperativity, and whether the presence of cooperative channels has an impact on encoding properties of neuronal populations. To address these questions we have constructed a conductance-based neuron model in which we continuously varied the size of a fraction [Formula: see text] of sodium channels expressing cooperativity and the strength of coupling between cooperative channels [Formula: see text]. We show that starting at a critical value of the coupling strength [Formula: see text], the activation curve of sodium channels develops a discontinuity at which opening of all coupled channels becomes an all-or-none event, leading to very rapid AP onsets. Models with a small fraction, [Formula: see text], of strongly cooperative channels generate APs with the most rapid onset dynamics. In this regime APs are triggered by simultaneous opening of the cooperative channel fraction and exhibit a pronounced biphasic waveform often observed in cortical neurons. We further show that presence of a small fraction of cooperative Na+ channels significantly improves the ability of neuronal populations to phase-lock their firing to high frequency input fluctuation. We conclude that presence of a small fraction of strongly coupled sodium channels can explain characteristic features of cortical APs and has a functional impact of enhancing the spike encoding of rapidly varying signals.

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Cooperative gating of  and  channels.(A) Simultaneous openings of pairs and triples of  channels in inside-out patch from cardiac myocytes treated with the ischaemic metabolite lysophosphatidylchloline [2]. In the left panel, zero corresponds to closed state; dotted lines and numbers 1,2,3 indicate openings to single, double and triple unitary conductance levels. Right panel shows histogram of current amplitude distribution. Note frequent occurrence of openings to double and triple unitary levels, but no openings to the unitary level. (B) Coopled gating of ryanodine R2  channels in cardiac cells [6]. Left panel shows example traces with openings to single, double and triple unitary conductance levels. Closed state is indicated by c; single, double and triple unitary conductance levels are indicated by 1,2,3. Right panel shows current amplitude histograms, corresponding to the traces on the left. Reproduced with permision from [2] and [6].
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pone-0037629-g001: Cooperative gating of and channels.(A) Simultaneous openings of pairs and triples of channels in inside-out patch from cardiac myocytes treated with the ischaemic metabolite lysophosphatidylchloline [2]. In the left panel, zero corresponds to closed state; dotted lines and numbers 1,2,3 indicate openings to single, double and triple unitary conductance levels. Right panel shows histogram of current amplitude distribution. Note frequent occurrence of openings to double and triple unitary levels, but no openings to the unitary level. (B) Coopled gating of ryanodine R2 channels in cardiac cells [6]. Left panel shows example traces with openings to single, double and triple unitary conductance levels. Closed state is indicated by c; single, double and triple unitary conductance levels are indicated by 1,2,3. Right panel shows current amplitude histograms, corresponding to the traces on the left. Reproduced with permision from [2] and [6].

Mentions: Ion channels are integral membrane proteins which, depending on conformation, can pass ionic currents and thus induce dynamic changes in membrane potential [1]. In voltage gated channels, permeability for ions is controlled by the membrane potential, introducing a fundamental nonlinearity in electrical signaling in neurons and muscle cells. An avalanche-like opening of voltage gated channels produces in these cells pulse-like electrical signals, action potentials (APs), which underlie the information processing capabilities of neurons. Biophysical models for AP generation almost universally assume that individual channels open and close statistically independently and are coupled only through the transmembrane voltage. However, channels for physiologically important cations (, , ) have been found capable of cooperative gating when clustered [2]–[8]. Fig. 1 shows examples of coupled gating of sodium and calcium channels in cardiac myocytes. Sodium channels express coupled gating after treatment with the ischaemic metabolite lysophosphatidylchloline [2] (Fig. 1A). Coupled gating of pairs and triplets of channels was reported for ryanodin R2 channels that lead to release of calcium from sarcoplasmic reticulum in cardiac cells [6] (Fig. 1B). In both examples, transitions between zero and conductance levels corresponding to opening of 2–3 channels occur more frequently than transitions to single-channel conductance level, indicating coupled gating of 2–3 channels. For potassium channels, coupled gating of up to 5 channels has been reported [3].


A small fraction of strongly cooperative sodium channels boosts neuronal encoding of high frequencies.

Huang M, Volgushev M, Wolf F - PLoS ONE (2012)

Cooperative gating of  and  channels.(A) Simultaneous openings of pairs and triples of  channels in inside-out patch from cardiac myocytes treated with the ischaemic metabolite lysophosphatidylchloline [2]. In the left panel, zero corresponds to closed state; dotted lines and numbers 1,2,3 indicate openings to single, double and triple unitary conductance levels. Right panel shows histogram of current amplitude distribution. Note frequent occurrence of openings to double and triple unitary levels, but no openings to the unitary level. (B) Coopled gating of ryanodine R2  channels in cardiac cells [6]. Left panel shows example traces with openings to single, double and triple unitary conductance levels. Closed state is indicated by c; single, double and triple unitary conductance levels are indicated by 1,2,3. Right panel shows current amplitude histograms, corresponding to the traces on the left. Reproduced with permision from [2] and [6].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3362627&req=5

pone-0037629-g001: Cooperative gating of and channels.(A) Simultaneous openings of pairs and triples of channels in inside-out patch from cardiac myocytes treated with the ischaemic metabolite lysophosphatidylchloline [2]. In the left panel, zero corresponds to closed state; dotted lines and numbers 1,2,3 indicate openings to single, double and triple unitary conductance levels. Right panel shows histogram of current amplitude distribution. Note frequent occurrence of openings to double and triple unitary levels, but no openings to the unitary level. (B) Coopled gating of ryanodine R2 channels in cardiac cells [6]. Left panel shows example traces with openings to single, double and triple unitary conductance levels. Closed state is indicated by c; single, double and triple unitary conductance levels are indicated by 1,2,3. Right panel shows current amplitude histograms, corresponding to the traces on the left. Reproduced with permision from [2] and [6].
Mentions: Ion channels are integral membrane proteins which, depending on conformation, can pass ionic currents and thus induce dynamic changes in membrane potential [1]. In voltage gated channels, permeability for ions is controlled by the membrane potential, introducing a fundamental nonlinearity in electrical signaling in neurons and muscle cells. An avalanche-like opening of voltage gated channels produces in these cells pulse-like electrical signals, action potentials (APs), which underlie the information processing capabilities of neurons. Biophysical models for AP generation almost universally assume that individual channels open and close statistically independently and are coupled only through the transmembrane voltage. However, channels for physiologically important cations (, , ) have been found capable of cooperative gating when clustered [2]–[8]. Fig. 1 shows examples of coupled gating of sodium and calcium channels in cardiac myocytes. Sodium channels express coupled gating after treatment with the ischaemic metabolite lysophosphatidylchloline [2] (Fig. 1A). Coupled gating of pairs and triplets of channels was reported for ryanodin R2 channels that lead to release of calcium from sarcoplasmic reticulum in cardiac cells [6] (Fig. 1B). In both examples, transitions between zero and conductance levels corresponding to opening of 2–3 channels occur more frequently than transitions to single-channel conductance level, indicating coupled gating of 2–3 channels. For potassium channels, coupled gating of up to 5 channels has been reported [3].

Bottom Line: Models with a small fraction, [Formula: see text], of strongly cooperative channels generate APs with the most rapid onset dynamics.In this regime APs are triggered by simultaneous opening of the cooperative channel fraction and exhibit a pronounced biphasic waveform often observed in cortical neurons.We conclude that presence of a small fraction of strongly coupled sodium channels can explain characteristic features of cortical APs and has a functional impact of enhancing the spike encoding of rapidly varying signals.

View Article: PubMed Central - PubMed

Affiliation: Max-Planck-Institute for Dynamics and Self-Organization, Bernstein Center for Computational Neuroscience, and Faculty of Physics, Georg August University School of Science, Göttingen, Germany.

ABSTRACT
Generation of action potentials (APs) is a crucial step in neuronal information processing. Existing biophysical models for AP generation almost universally assume that individual voltage-gated sodium channels operate statistically independently, and their avalanche-like opening that underlies AP generation is coordinated only through the transmembrane potential. However, biological ion channels of various types can exhibit strongly cooperative gating when clustered. Cooperative gating of sodium channels has been suggested to explain rapid onset dynamics and large threshold variability of APs in cortical neurons. It remains however unknown whether these characteristic properties of cortical APs can be reproduced if only a fraction of channels express cooperativity, and whether the presence of cooperative channels has an impact on encoding properties of neuronal populations. To address these questions we have constructed a conductance-based neuron model in which we continuously varied the size of a fraction [Formula: see text] of sodium channels expressing cooperativity and the strength of coupling between cooperative channels [Formula: see text]. We show that starting at a critical value of the coupling strength [Formula: see text], the activation curve of sodium channels develops a discontinuity at which opening of all coupled channels becomes an all-or-none event, leading to very rapid AP onsets. Models with a small fraction, [Formula: see text], of strongly cooperative channels generate APs with the most rapid onset dynamics. In this regime APs are triggered by simultaneous opening of the cooperative channel fraction and exhibit a pronounced biphasic waveform often observed in cortical neurons. We further show that presence of a small fraction of cooperative Na+ channels significantly improves the ability of neuronal populations to phase-lock their firing to high frequency input fluctuation. We conclude that presence of a small fraction of strongly coupled sodium channels can explain characteristic features of cortical APs and has a functional impact of enhancing the spike encoding of rapidly varying signals.

Show MeSH
Related in: MedlinePlus