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@article{807509,
author = {Christé, Georges and Chahine, Mohamed and Chevalier, Philippe and Pásek, Michal},
article_location = {Great Britain},
article_number = {1-3},
keywords = {cardiac cell; SCN5A mutation; Long QT syndrome; quantitative modelling},
language = {eng},
issn = {0079-6107},
journal = {Progress in Biophysics and Molecular Biology},
title = {Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3},
volume = {96},
year = {2008}
}
TY - JOUR
ID - 807509
AU - Christé, Georges - Chahine, Mohamed - Chevalier, Philippe - Pásek, Michal
PY - 2008
TI - Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3
JF - Progress in Biophysics and Molecular Biology
VL - 96
IS - 1-3
SP - 281-293
EP - 281-293
PB - Elsevier Ltd.
SN - 00796107
KW - cardiac cell
KW - SCN5A mutation
KW - Long QT syndrome
KW - quantitative modelling
N2 - In LQT3 patients, SCN5A mutations induce ultraslow inactivation of a small fraction of the hNav1.5 current, i.e. persistent Na+ current (IpNa). We explored the time course of effects of such a change on the intracellular ionic homeostasis in a model of guinea pig cardiac ventricular cell [Pasek, M., Simurda, J., Orchard, C.H., Christe, G., 2007b. A model of the guinea pig ventricular cardiomyocyte incorporating a transverse axial tubular system. Prog. Biophys. Mol. Biol., this issue]. Sudden addition of IpNa prevented action potential (AP) repolarization when its conductance (gpNa) exceeded 0.12% of the maximal conductance of fast INa (gNa). With gpNa at 0.1% gNa, the AP duration at 90% repolarization (APD90) was initially lengthened to 2.6-fold that in control. Under regular stimulation at 1Hz it shortened progressively to 1.37-fold control APD90, and intracellular [Na+]i increased by 6% with a time constant of 106 s. Further increasing gpNa to 0.2% gNa caused an immediate increase in APD90 to 5.7-fold that in control, which decreased to 2.2-fold that in control in 30 s stimulation at 1 Hz. At this time diastolic [Na+]i and [Ca2+]i were, respectively, 34% and 52% higher than in control and spontaneous erratic SR Ca release occurred. In the presence of IpNa causing 46% lengthening of APD90, the model cell displayed arrhythmogenic behaviour whenexternal [K+] was lowered to 5mM from an initial value at 5.4mM. By contrast, when K+ currents IKr and IKs were lowered in the model cell to produce the same lengthening of APD90, no proarrhythmic behaviour was observed, even when external [K+] was lowered to 2.5 mM.
ER -
CHRISTÉ, Georges, Mohamed CHAHINE, Philippe CHEVALIER and Michal PÁSEK. Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3. \textit{Progress in Biophysics and Molecular Biology}. Great Britain: Elsevier Ltd., 2008, vol.~96, 1-3, p.~281-293, 12 pp. ISSN~0079-6107.
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