EXCITABILITY AND REPOLARIZATION IN AN IONIC MODEL OF THE CARDIAC CELL-MEMBRANE

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 eq uivalents. The modified Beeler-Reuter model (MBR) of the ventricular m embrane was selected for this purpose because its action potential ups troke, plateau and repolarization phase occur along sufficiently well separated timescales. The information on the MBR model dynamics was ob tained by premature stimulation at various coupling intervals, under s table conditions of regular pacing at different cycle lengths. A gener al method was developed to study the threshold behaviour of the system . As a first step, a pair of complementary threshold criteria was defi ned in terms of peak ionic current and time to repolarization in order to reliably distinguish between classes of sub-threshold and supra-th reshold responses. One of the main conclusions is that the activation of the MBR model by short-duration stimuli (< 5 msec) can be accuratel y represented by a one-variable or a two-variable dynamic equivalent. In addition, because of the large surge of Na+ current at threshold, t he recovery of excitability is essentially independent of the conditio ning action potential waveform (no threshold-memory effect). Another m ajor result pertains to the higher complexity of the repolarization pr ocess, stressing the critical role played by the activation dynamics o f the secondary inward current. There is a substantial dependence of t he action potential duration (APD) on the conditioning action potentia l waveform (APD-memory effect), and at least a three-variable model is necessary for a reasonable approximation.