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The arrhythmogenic role of stretch‐activated channels in rat atrial myocytes
Author(s) -
Youm Jae Boum,
Leem Chae Hun,
Han Jin,
Earm Yung E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.971.11
Subject(s) - diastolic depolarization , depolarization , biophysics , chemistry , myocyte , intracellular , membrane potential , calcium , atrial myocytes , sodium channel , sodium calcium exchanger , calcium in biology , electrophysiology , medicine , sodium , biology , sinoatrial node , biochemistry , heart rate , organic chemistry , blood pressure
Since their first discovery 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 such as ionic selectivity and stretch‐dependence have been studied both in the single‐channel and at the whole‐cell level. There is growing evidence that major stretch‐induced changes in electrical activity are mediated by activation of these channels. The involvement of SACs in stretch‐induced arrhythmias and diastolic depolarization was demonstrated using a specific blocker. Noma's group has created a cardiac cell model (Kyoto‐Model) to describe various cellular activities such as the action potential, Ca2+ transients and contractile force. We focus on the possible contribution of SACs to the generation of atrial rhythm disturbances by combining the Kyoto‐Model and experimental findings on SACs in rat atrial myocytes. The simulation shows that the SACs trigger the firing of action potentials by depolarizing the cell membrane to reach the threshold for the activation of voltage‐gated sodium channel and that the firing ceases when a significant rise in intracellular sodium concentration develops. The simulation also shows that the delayed increase in the intracellular calcium concentration triggers the calcium‐induced calcium release and that the subsequent activation of Na+/Ca2+ exchanger drives spontaneous firing of action potentials. These simulation results successfully demonstrate how the SACs can drive the generation of stretch‐induced arrhythmias such as atrial tachycardia and atrial fibrillation.