Mechanism for action potential alternans: The interplay between L-type calcium current and transient outward current
Mechanism for action potential alternans: The interplay between L-type calcium current and transient outward current
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DOI：
10.1016/j.hrthm.2005.11.016
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发表时间：
2006-03-01
期刊：
影响因子：
5.5
通讯作者：
Hopenfeld, B
中科院分区：
文献类型：
--
作者：
Hopenfeld, B
背景动作电位时程交替的离子机制尚未建立。目的本研究的目的是探索动作电位交替的机制。方法使用单个缺血心肌细胞模型进行计算机模拟。为了模拟缺血，细胞外钾升高到10 mM，L-型钙通道电导率下降，和瞬时外向电流I-的电导率是varied.Results交替发生在350和1,800毫秒之间的基本周期长度。交替导致的钙和瞬时外向电流失活门的恢复动力学的相互作用。根据舒张间期，瞬时外向电流足够强，钙电流足够弱，导致动作电位平台消失，从而导致动作电位缩短。失活门的失活和恢复动力学是这样的，即在缩短的动作电位后，钙电流相对强于瞬时外向电流。随后的动作电位是长的，因为钙电流足够大，以恢复动作电位平台圆顶后，部分复极化所造成的瞬态外向电流。多空格局无限期重复。这种交替机制解释了2：1模式如何演变成3：1模式，在至少一个实验中观察到，缺血的进展和钙电流intimes.CONCLUSION计算机模拟和基本理论表明，L-型钙和瞬时外向电流之间的相互作用，导致至少一种类型的交替。
BACKGROUND The ionic mechanisms underlying action potential duration alternans are not established.OBJECTIVES The purpose of this study was to explore the mechanisms underlying action potential alternans.METHODS Computer simulations were performed using a model of a single ischemic myocyte. To emulate ischemia, extracellular potassium was raised to 10 mM, L-type calcium channel conductance was decreased, and the conductivity of the transient outward current I-to was varied.RESULTS Alternans occurred at basic cycle lengths between 350 and 1,800 ms. The alternans resulted from the interplay of the recovery kinetics of the calcium and transient outward current inactivation gates. Depending on the diastolic interval, the transient outward current was sufficiently strong and calcium current sufficiently weak to result in the abolition of the action potential plateau and thus in an abbreviated action potential. The inactivation and recovery kinetics of the inactivation gates were such that calcium current was relatively stronger than transient outward current after an abbreviated action potential. The subsequent action potential was long because calcium current was sufficiently large to restore the action potential plateau dome after the partial repolarization caused by the transient outward current. The long-short pattern repeated indefinitely. This alternans mechanism explains how 2:1 patterns can evolve into 3:1 patterns, as observed in at least one experiment, as ischemia progresses and calcium current diminishes.CONCLUSION Computer simulations and basic theory suggest that the interplay between L-type calcium and transient outward currents causes at least one type of alternans.