Galice Samuel, Bers Donald M, Sato Daisuke
Department of Pharmacology, University of California, Davis, Davis, California.
Department of Pharmacology, University of California, Davis, Davis, California.
Biophys J. 2016 Jun 21;110(12):2671-2677. doi: 10.1016/j.bpj.2016.05.026.
Cardiac alternans has been linked to the onset of ventricular fibrillation and ventricular tachycardia, leading to life-threatening arrhythmias. Here, we investigated the effects of stretch-activated currents (ISAC) on alternans using a physiologically detailed model of the ventricular myocyte. We found that increasing ISAC suppresses alternans if the voltage-Ca coupling is positive or the alternans is voltage driven. However, for electromechanically discordant alternans, which occurs when the alternans is Ca driven with negative voltage-Ca coupling, increasing ISAC promotes Ca alternans. In addition, if action potential duration-Ca transients show quasiperiodicity, we observe a biphasic effect of ISAC, i.e., suppressing quasiperiodic oscillation at small stretch but promoting electromechanically discordant alternans at larger stretch. Our results demonstrate how ISAC interacts with coupled voltage-Ca dynamical systems with respect to alternans.
心脏交替性与室颤和室性心动过速的发作有关,可导致危及生命的心律失常。在此,我们使用心室肌细胞的生理详细模型研究了牵张激活电流(ISAC)对交替性的影响。我们发现,如果电压 - 钙耦合为正或交替性由电压驱动,增加ISAC可抑制交替性。然而,对于当交替性由钙驱动且电压 - 钙耦合为负时出现的机电不一致性交替性,增加ISAC会促进钙交替性。此外,如果动作电位时程 - 钙瞬变表现为准周期性,我们观察到ISAC的双相效应,即在小牵张时抑制准周期性振荡,但在大牵张时促进机电不一致性交替性。我们的结果证明了ISAC在交替性方面如何与耦合的电压 - 钙动力学系统相互作用。