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Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

机译:拉伸诱发大鼠心房肌细胞致心律失常的模型

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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.
机译:自从在小鸡的骨骼肌中首次发现以来,就已经提出了拉伸激活通道(SAC)作为在细胞水平上机械刺激的可能的机械换能器。已经在单通道和整个小区级别研究了通道特性。越来越多的证据表明,主要的拉伸诱导的电活动变化是由这些通道的激活介导的。我们旨在通过利用大鼠心房肌细胞的最新数学模型来研究拉伸诱导的自发性机制,该模型已建立来复制细胞活动,例如动作电位,Ca 2 + 瞬变和收缩力。根据实验结果,将SAC纳入数学模型,成功地再现了通过拉伸重复发射自发动作电位的过程。诱导的自动化包括两个阶段。早期由电压门控Na + 通道的背景电导增加驱动,而后期则由Na + / Ca 和Ca 2 + 产生的> 2 + 交换电流。这些模拟结果成功地证明了SAC如何在单个心房肌细胞中诱导自发性,这可能是与心脏其他心律失常变化相协调而引发和维持房颤的焦点。

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