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Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics
Exploring the properties of action potentials is a crucial step toward a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028613/ https://www.ncbi.nlm.nih.gov/pubmed/29997481 http://dx.doi.org/10.3389/fncel.2018.00187 |
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author | Almog, Mara Barkai, Tal Lampert, Angelika Korngreen, Alon |
author_facet | Almog, Mara Barkai, Tal Lampert, Angelika Korngreen, Alon |
author_sort | Almog, Mara |
collection | PubMed |
description | Exploring the properties of action potentials is a crucial step toward a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. However, most models of voltage-gated sodium channels assume a concerted Hodgkin and Huxley kinetic gating scheme. However, it is not clear if Hodgkin and Huxley models are suitable for use in action potential simulations of central nervous system neurons. To resolve this, we investigated the activation kinetics of voltage-gated sodium channels. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. Thus, the classical Hodgkin and Huxley description of sodium channel kinetics may be unsuitable for modeling the physiological role of this channel. Furthermore, our results reconcile between apparently contradicting studies sodium channel activation. Our findings may have key implications for the role of sodium channels in synaptic integration and action potential generation. |
format | Online Article Text |
id | pubmed-6028613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60286132018-07-11 Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics Almog, Mara Barkai, Tal Lampert, Angelika Korngreen, Alon Front Cell Neurosci Neuroscience Exploring the properties of action potentials is a crucial step toward a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. However, most models of voltage-gated sodium channels assume a concerted Hodgkin and Huxley kinetic gating scheme. However, it is not clear if Hodgkin and Huxley models are suitable for use in action potential simulations of central nervous system neurons. To resolve this, we investigated the activation kinetics of voltage-gated sodium channels. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. Thus, the classical Hodgkin and Huxley description of sodium channel kinetics may be unsuitable for modeling the physiological role of this channel. Furthermore, our results reconcile between apparently contradicting studies sodium channel activation. Our findings may have key implications for the role of sodium channels in synaptic integration and action potential generation. Frontiers Media S.A. 2018-06-26 /pmc/articles/PMC6028613/ /pubmed/29997481 http://dx.doi.org/10.3389/fncel.2018.00187 Text en Copyright © 2018 Almog, Barkai, Lampert and Korngreen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Almog, Mara Barkai, Tal Lampert, Angelika Korngreen, Alon Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title | Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title_full | Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title_fullStr | Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title_full_unstemmed | Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title_short | Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics |
title_sort | voltage-gated sodium channels in neocortical pyramidal neurons display cole-moore activation kinetics |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028613/ https://www.ncbi.nlm.nih.gov/pubmed/29997481 http://dx.doi.org/10.3389/fncel.2018.00187 |
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