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KMID : 0811720080120050267
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Korean Journal of Physiology & Pharmacology
2008 Volume.12 No. 5 p.267 ~ p.274
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Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes
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Youm Jae-Boum
Kim Na-Ri
Han Jin
Leem Chae-Hun
Earm Yung-E
Zhang Yin-Hua
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Abstract
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Since first discovered in chick skeletal muscles, stretch-activated channels (SACs) have been proposed as a probable mechano-transducer of the mechanical stimulus at the cellular level. Channel properties have been studied in both the single-channel and the whole-cell level. There is growing evidence to indicate that major stretch-induced changes in electrical activity are mediated by activation of these channels. We aimed to investigate the mechanism of stretch-induced automaticity by exploiting a recent mathematical model of rat atrial myocytes which had been established to reproduce cellular activities such as the action potential, Ca2＋ transients, and contractile force. The incorporation of SACs into the mathematical model, based on experimental results, successfully reproduced the repetitive firing of spontaneous action potentials by stretch. The induced automaticity was composed of two phases. The early phase was driven by increased background conductance of voltage-gated Na＋ channel, whereas the later phase was driven by the reverse-mode operation of Na＋/Ca2＋ exchange current secondary to the accumulation of Na＋ and Ca2＋ through SACs. These results of simulation successfully demonstrate how the SACs can induce automaticity in a single atrial myocyte which may act as a focus to initiate and maintain atrial fibrillation in concert with other arrhythmogenic changes in the heart.
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KEYWORD
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Stretch, Automaticity, Atrial fibrillation, Modeling
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