Action potential and contractility changes in [Na+]i overloaded cardiac myocytes:: A simulation study
Action potential and contractility changes in [Na+]i overloaded cardiac myocytes:: A simulation study
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DOI：
10.1016/s0006-3495(00)76783-x
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发表时间：
2000-05-01
影响因子：
3.4
通讯作者：
Rudy, Y
中科院分区：
文献类型：
--
作者：
Faber, GM;Rudy, Y
心肌细胞的钠超载可伴随多种病理变化并诱发致命性心律失常。我们使用哺乳动物心室肌细胞的Luo-Rudy模型研究细胞内钠升高对心脏动作电位（AP）和细胞内钙的影响。其结果是：1）在快速起搏过程中，AP持续时间（APD）缩短分为两个阶段，快速阶段没有Na+积聚，较慢阶段取决于[Na+]（i）。2)APD的快速缩短是由于I-Ks的不完全失活（积累）。3)慢相直接导致复极化电流I-NaK和反向电流I-NaCa的增加，继发于[Na+]（i）的升高。4)Na+超负荷减慢AP去极化速率，为更大的I-Ca（L）激活留出时间;它还增强了反向模式I-NaCa。由此产生的Ca 2+内流增加触发更大的[Ca 2 +]（i）瞬变。5)单独的反向模式I-NaCa可以以电压和[Na+]（i）依赖性方式触发Ca 2+释放。6)在I-NaK阻滞过程中，由于I-NaCa的增强，Na+和Ca 2+积累，APD缩短; I-K（Na）对APD缩短的贡献可以忽略不计。Na ~+超载通过减慢AP除极速度和缩短APD而增强折返性心律失常的诱发作用。APD缩短伴[Ca 2 +]升高（继发于Na+超负荷）也易使心肌发生致心律失常性延迟后除极。
Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na+ accumulation and a slower phase that depends on [Na+](i). 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of I-Ks. 3) The slow phase is dire to increased repolarizing currents I-NaK and reverse-mode I-NaCa, secondary to elevated [Na+](i). 4) Na+-overload slows the rate of AP depolarization, allowing time for greater I-Ca(L) activation; it also enhances reverse-mode I-NaCa. The resulting increased Ca2+ influx triggers a greater [Ca2+](i) transient. 5) Reverse-mode I-NaCa alone can trigger Ca2+ release in a voltage and [Na+](i)-dependent manner. 6) During I-NaK block, Na+ and Ca2+ accumulate and APD shortens due to enhanced reverse-mode I-NaCa; contribution of I-K(Na) to APD shortening is negligible. By slowing AP depolarization thence velocity) and shortening APD, Na+-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca2+], (secondary to Na+-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.