Vinet A, Roberge F A
Institute of Biomedical Engineering, Ecole Polytechnique Université de Montréal Canada.
J Theor Biol. 1994 Sep 21;170(2):183-99. doi: 10.1006/jtbi.1994.1178.
The main objective of this study was to investigate the possibility of expressing the activation and repolarization processes of a realistic ionic model of the myocyte membrane in terms of simplified dynamic equivalents. The modified Beeler-Reuter model (MBR) of the ventricular membrane was selected for this purpose because its action potential upstroke, plateau and selected for this purpose because its action potential upstroke, plateau and repolarization phase occur along sufficiently well separated timescales. The information on the MBR model dynamics was obtained by premature stimulation at various coupling intervals, under stable conditions of regular pacing at different cycle lengths. A general method was developed to study the threshold behavior of the system. As a first step, a pair of complementary threshold criteria was defined in terms of peak ionic current and time to repolarization in order to reliably distinguish between classes of sub-threshold and supra-threshold responses. Of the main conclusions is that the activation of the MBR model by short-duration stimuli (< 5 msec) can be accurately represented by a one-variable or a two-variable dynamic equivalent. In addition, because of the large surge of Na+ current at threshold, the recovery of excitability is essentially independent of the conditioning action potential waveform (no threshold-memory effect). Another major result pertains to the higher complexity of the repolarization process, stressing the critical role played by the activation dynamics of the secondary inward current. There is a substantial dependence of the action potential duration (APD) on the conditioning action potential waveform (APD-memory effect), and at least a three-variable model is necessary for a reasonable approximation.
本研究的主要目的是研究能否用简化的动态等效模型来表示心肌细胞膜真实离子模型的激活和复极过程。为此选择了心室膜的改良贝勒-罗伊特模型（MBR），因为其动作电位的上升支、平台期和复极期发生在时间尺度上有足够明显的分离。在不同周期长度的稳定起搏条件下，通过在不同耦合间隔下进行过早刺激来获取MBR模型动力学的信息。开发了一种通用方法来研究系统的阈值行为。第一步，根据离子电流峰值和复极时间定义了一对互补的阈值标准，以便可靠地区分阈下和阈上反应类别。主要结论之一是，短持续时间刺激（<5毫秒）对MBR模型的激活可以用单变量或双变量动态等效模型精确表示。此外，由于阈值处Na+电流的大幅激增，兴奋性的恢复基本上与条件动作电位波形无关（无阈值记忆效应）。另一个主要结果与复极过程的更高复杂性有关，强调了次级内向电流激活动力学所起的关键作用。动作电位持续时间（APD）对条件动作电位波形有很大依赖性（APD记忆效应），并且至少需要一个三变量模型才能进行合理近似。
