Nordin C
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H447-65. doi: 10.1152/ajpheart.1996.270.2.H447.
Single premature stimulations during trains of nondriven action potentials induced by depolarization normally cause a transient hyperpolarization of diastolic membrane potential before the subsequent spontaneous upstroke. However, rare, marked transient depolarizations have also been reported. This paper presents experimental data and computer simulations that characterize transient depolarization following premature stimulations and investigate the role of intracellular [Ca2+] in generating this unusual response. In isolated guinea pig myocytes, transient depolarizations (range 4-58 mV) consistently occurred following stimulations 100-160 ms after the upstroke of spontaneous action potentials during exposure to K(+)-free Tyrode solution, which raises intracellular [Ca2+]. In contrast, no transient depolarizations developed when stimulations were delivered during injection of constant inward current or brief exposure to very low dose of Ba2+ (250-500 microM). The experimental response to K(+)-free Tyrode solution was reproduced by a computer model of the transmembrane current and intracellular Ca2+ flux of an isolated guinea pig ventricular myocyte (24) following reduction of extracellular [K+] below 1 mM. Transient depolarization was generated primarily by Na/Ca exchange. Simulations using only those equations governing intracellular Ca2+ cycling revealed that bursts of Ca2+ into the myoplasm after Ca2+ loading caused a transient increase in trough myoplasmic [Ca2+] when the coupling interval following the upstroke of a myoplasmic [Ca2+] oscillation was nearly identical to those coupling intervals that caused pacing-induced transient depolarization of membrane potential after the upstroke of an action potential. These results suggest that transient depolarizations following nondriven action potentials arise from critically timed, stimulus-induced perturbation of intracellular [Ca2+] oscillations associated with Ca2+ overload. Simulations using a multicellular model suggest that critically timed premature stimulations can initiate trains of depolarized, nondriven action potentials in otherwise quiescent, Ca(2+)-overloaded heterogeneous syncytia by a similar mechanism.
在由去极化诱导的非驱动动作电位串期间的单个过早刺激通常会在随后的自发上升之前引起舒张期膜电位的短暂超极化。然而，也有罕见的、明显的短暂去极化的报道。本文展示了实验数据和计算机模拟，其描述了过早刺激后的短暂去极化，并研究了细胞内[Ca2+]在产生这种异常反应中的作用。在分离的豚鼠心肌细胞中，在暴露于无钾的台氏液（其会升高细胞内[Ca2+]）期间，在自发动作电位上升后100 - 160毫秒进行刺激后，持续出现短暂去极化（范围为4 - 58毫伏）。相反，在注入恒定内向电流期间或短暂暴露于非常低剂量的Ba2+（250 - 500微摩尔）期间进行刺激时，未出现短暂去极化。通过将细胞外[K+]降低至1毫摩尔以下后，分离的豚鼠心室肌细胞的跨膜电流和细胞内Ca2+通量的计算机模型（24）再现了对无钾台氏液的实验反应。短暂去极化主要由钠钙交换产生。仅使用那些控制细胞内Ca2+循环的方程式进行的模拟显示，在Ca2+加载后Ca2+爆发进入肌浆时，当肌浆[Ca2+]振荡上升后的耦合间隔与那些在动作电位上升后引起起搏诱导的膜电位短暂去极化的耦合间隔几乎相同时，肌浆谷底[Ca2+]会短暂增加。这些结果表明，非驱动动作电位后的短暂去极化源于与Ca2+过载相关的细胞内[Ca2+]振荡的临界定时、刺激诱导的扰动。使用多细胞模型的模拟表明，临界定时的过早刺激可通过类似机制在原本静止的、Ca(2+)过载的异质合体中引发去极化的、非驱动动作电位串。
