Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.

<h4>Background</h4>The SCN5A encoded sodium current (I(Na)) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of I(Na) with near-phy...

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Autores principales:	Géza Berecki, Ronald Wilders, Berend de Jonge, Antoni C G van Ginneken, Arie O Verkerk
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0dc9df0c1b414cd48ec6774fcc1d6f90
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spelling	oai:doaj.org-article:0dc9df0c1b414cd48ec6774fcc1d6f902021-11-18T07:00:49ZRe-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.1932-620310.1371/journal.pone.0015772https://doaj.org/article/0dc9df0c1b414cd48ec6774fcc1d6f902010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21217835/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The SCN5A encoded sodium current (I(Na)) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of I(Na) with near-physiological ion concentrations and temperature is technically challenging due to the large amplitude and rapidly activating nature of I(Na), which may seriously hamper the quality of voltage control over the membrane. We hypothesized that the alternating voltage clamp-current clamp (VC/CC) technique might provide an alternative to traditional voltage clamp (VC) technique for the determination of I(Na) properties under physiological conditions.<h4>Principal findings</h4>We studied I(Na) under close-to-physiological conditions by VC technique in SCN5A cDNA-transfected HEK cells or by alternating VC/CC technique in both SCN5A cDNA-transfected HEK cells and rabbit left ventricular myocytes. In these experiments, peak I(Na) during a depolarizing VC step or maximal upstroke velocity, dV/dt(max), during VC/CC served as an indicator of available I(Na). In HEK cells, biophysical properties of I(Na), including current density, voltage dependent (in)activation, development of inactivation, and recovery from inactivation, were highly similar in VC and VC/CC experiments. As an application of the VC/CC technique we studied I(Na) in left ventricular myocytes isolated from control or failing rabbit hearts.<h4>Conclusions</h4>Our results demonstrate that the alternating VC/CC technique is a valuable experimental tool for I(Na) measurements under close-to-physiological conditions in cardiac myocytes.Géza BereckiRonald WildersBerend de JongeAntoni C G van GinnekenArie O VerkerkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15772 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Géza Berecki Ronald Wilders Berend de Jonge Antoni C G van Ginneken Arie O Verkerk Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
description	<h4>Background</h4>The SCN5A encoded sodium current (I(Na)) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of I(Na) with near-physiological ion concentrations and temperature is technically challenging due to the large amplitude and rapidly activating nature of I(Na), which may seriously hamper the quality of voltage control over the membrane. We hypothesized that the alternating voltage clamp-current clamp (VC/CC) technique might provide an alternative to traditional voltage clamp (VC) technique for the determination of I(Na) properties under physiological conditions.<h4>Principal findings</h4>We studied I(Na) under close-to-physiological conditions by VC technique in SCN5A cDNA-transfected HEK cells or by alternating VC/CC technique in both SCN5A cDNA-transfected HEK cells and rabbit left ventricular myocytes. In these experiments, peak I(Na) during a depolarizing VC step or maximal upstroke velocity, dV/dt(max), during VC/CC served as an indicator of available I(Na). In HEK cells, biophysical properties of I(Na), including current density, voltage dependent (in)activation, development of inactivation, and recovery from inactivation, were highly similar in VC and VC/CC experiments. As an application of the VC/CC technique we studied I(Na) in left ventricular myocytes isolated from control or failing rabbit hearts.<h4>Conclusions</h4>Our results demonstrate that the alternating VC/CC technique is a valuable experimental tool for I(Na) measurements under close-to-physiological conditions in cardiac myocytes.
format	article
author	Géza Berecki Ronald Wilders Berend de Jonge Antoni C G van Ginneken Arie O Verkerk
author_facet	Géza Berecki Ronald Wilders Berend de Jonge Antoni C G van Ginneken Arie O Verkerk
author_sort	Géza Berecki
title	Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
title_short	Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
title_full	Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
title_fullStr	Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
title_full_unstemmed	Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.
title_sort	re-evaluation of the action potential upstroke velocity as a measure of the na+ current in cardiac myocytes at physiological conditions.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0dc9df0c1b414cd48ec6774fcc1d6f90
work_keys_str_mv	AT gezaberecki reevaluationoftheactionpotentialupstrokevelocityasameasureofthenacurrentincardiacmyocytesatphysiologicalconditions AT ronaldwilders reevaluationoftheactionpotentialupstrokevelocityasameasureofthenacurrentincardiacmyocytesatphysiologicalconditions AT berenddejonge reevaluationoftheactionpotentialupstrokevelocityasameasureofthenacurrentincardiacmyocytesatphysiologicalconditions AT antonicgvanginneken reevaluationoftheactionpotentialupstrokevelocityasameasureofthenacurrentincardiacmyocytesatphysiologicalconditions AT arieoverkerk reevaluationoftheactionpotentialupstrokevelocityasameasureofthenacurrentincardiacmyocytesatphysiologicalconditions
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Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.

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