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 a Michal PÁSEK

Základní údaje

Originální název

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

Název česky

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

Autoři

CHRISTÉ, Georges; Mohamed CHAHINE; Philippe CHEVALIER a Michal PÁSEK

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 6.388

Organizační jednotka

Lékařská fakulta

UT WoS

000254598000016

Klíčová slova anglicky

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

Štítky

Cardiac cell, long QT syndrome, Quantitative modelling, SCN5A mutation

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 6. 2009 15:52, doc. Ing. Michal Pásek, Ph.D.

Anotace

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.

Česky

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

Citovat

CHRISTÉ, Georges; Mohamed CHAHINE; Philippe CHEVALIER a 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, roč. 96, 1-3, s. 281-293, 12 s. 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 a 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, roč.~96, 1-3, s.~281-293, 12 s. ISSN~0079-6107.

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