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Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4

The number of voltage-gated sodium (Na(V)) channels available to generate action potentials in muscles and nerves is adjusted over seconds to minutes by prior electrical activity, a process called slow inactivation (SI). The basis for SI is uncertain. Na(V) channels have four domains (DI–DIV), each...

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Autores principales: Silva, Jonathan R., Goldstein, Steve A.N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581692/
https://www.ncbi.nlm.nih.gov/pubmed/23401571
http://dx.doi.org/10.1085/jgp.201210909
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author Silva, Jonathan R.
Goldstein, Steve A.N.
author_facet Silva, Jonathan R.
Goldstein, Steve A.N.
author_sort Silva, Jonathan R.
collection PubMed
description The number of voltage-gated sodium (Na(V)) channels available to generate action potentials in muscles and nerves is adjusted over seconds to minutes by prior electrical activity, a process called slow inactivation (SI). The basis for SI is uncertain. Na(V) channels have four domains (DI–DIV), each with a voltage sensor that moves in response to depolarizing stimulation over milliseconds to activate the channels. Here, SI of the skeletal muscle channel Na(V)1.4 is induced by repetitive stimulation and is studied by recording of sodium currents, gating currents, and changes in the fluorescence of probes on each voltage sensor to assess their movements. The magnitude, voltage dependence, and time course of the onset and recovery of SI are observed to correlate with voltage-sensor movements 10,000-fold slower than those associated with activation. The behavior of each voltage sensor is unique. Development of SI over 1–160 s correlates best with slow immobilization of the sensors in DI and DII; DIII tracks the onset of SI with less fidelity. Showing linkage to the sodium conduction pathway, pore block by tetrodotoxin affects both SI and immobilization of all the sensors, with DI and DII significantly suppressed. Recovery from SI correlates best with slow restoration of mobility of the sensor in DIII. The findings suggest that voltage-sensor movements determine SI and thereby mediate Na(V) channel availability.
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spelling pubmed-35816922013-09-01 Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4 Silva, Jonathan R. Goldstein, Steve A.N. J Gen Physiol Research Article The number of voltage-gated sodium (Na(V)) channels available to generate action potentials in muscles and nerves is adjusted over seconds to minutes by prior electrical activity, a process called slow inactivation (SI). The basis for SI is uncertain. Na(V) channels have four domains (DI–DIV), each with a voltage sensor that moves in response to depolarizing stimulation over milliseconds to activate the channels. Here, SI of the skeletal muscle channel Na(V)1.4 is induced by repetitive stimulation and is studied by recording of sodium currents, gating currents, and changes in the fluorescence of probes on each voltage sensor to assess their movements. The magnitude, voltage dependence, and time course of the onset and recovery of SI are observed to correlate with voltage-sensor movements 10,000-fold slower than those associated with activation. The behavior of each voltage sensor is unique. Development of SI over 1–160 s correlates best with slow immobilization of the sensors in DI and DII; DIII tracks the onset of SI with less fidelity. Showing linkage to the sodium conduction pathway, pore block by tetrodotoxin affects both SI and immobilization of all the sensors, with DI and DII significantly suppressed. Recovery from SI correlates best with slow restoration of mobility of the sensor in DIII. The findings suggest that voltage-sensor movements determine SI and thereby mediate Na(V) channel availability. The Rockefeller University Press 2013-03 /pmc/articles/PMC3581692/ /pubmed/23401571 http://dx.doi.org/10.1085/jgp.201210909 Text en © 2013 Silva and Goldstein https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) ).
spellingShingle Research Article
Silva, Jonathan R.
Goldstein, Steve A.N.
Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title_full Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title_fullStr Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title_full_unstemmed Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title_short Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: Wild-type skeletal muscle Na(V)1.4
title_sort voltage-sensor movements describe slow inactivation of voltage-gated sodium channels i: wild-type skeletal muscle na(v)1.4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581692/
https://www.ncbi.nlm.nih.gov/pubmed/23401571
http://dx.doi.org/10.1085/jgp.201210909
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