Changes in action potentials and intracellular ionic
homeostasis in a ventricular cell model related to a persistent
sodium current in SCN5A mutations underlying LQT3

J 2008

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

CHRISTÉ, Georges, Mohamed CHAHINE, Philippe CHEVALIER and Michal PÁSEK

Basic information

Original name

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

Name in Czech

Změny akčního napětí a intracelulární iontové homeostázy vyvolané perzistentním sodíkovým proudem u modelu komorové buňky při SCN5A mutaci podmiňující LQT3

Authors

CHRISTÉ, Georges, Mohamed CHAHINE, Philippe CHEVALIER and Michal PÁSEK

Edition

Progress in Biophysics and Molecular Biology, Great Britain, Elsevier Ltd. 2008, 0079-6107

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.388

Organization unit

Faculty of Medicine

UT WoS

000254598000016

Keywords in English

cardiac cell; SCN5A mutation; Long QT syndrome; quantitative modelling

Abstract

ORIG CZ

V originále

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.

In Czech

Předmětem práce je vyšetření fyziologických důsledků SCN5A mutace sodíkového kanálu u srdečních komorových buněk pomoci matematického modelu.

Citovat

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. Progress in Biophysics and Molecular Biology. Great Britain: Elsevier Ltd., 2008, vol. 96, 1-3, p. 281-293, 12 pp. ISSN 0079-6107.

@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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