Effect of strength and timing of transmembrane current pulses on isolated ventricular myocytes

Cellular Response to Premature Stimuli. Introduction: Little is known about how the amplitude and timing of transmembrane current pulses affect transm embrane potential (V-m) and action potential duration (APD) in isolated myo cytes. Methods and Results: Ten ventricular myocytes were isolated from five rabbi t hearts. Each cell was paced at an S1 cycle length of 250 msec, and S2 pul ses of 10-msec duration were delivered at various strengths and time interv als. For all S2 strengths (0.2 to 1.5 nA), the magnitude of changes in V-m did not depend on polarity during the plateau, but were larger for depolari zing pulses during phase 3 repolarization. However, the magnitude of change s in APD varied with polarity during the entire action potential for streng ths ranging from 0.5 to 1.5 nA. Greater changes in APD occurred for hyperpo larizing pulses during the plateau and depolarizing pulses during phase 3. In addition, we used a cardiac phase variable to quantify the current thres hold for regenerative depolarization and repolarization as a function of pr estimulus V-m. Regenerative depolarization occurred during phase 3 repolari zation, and its current threshold was less than that required for regenerat ive repolarization that occurred during the plateau. These data were compar ed to computer simulations in a patch of membrane represented by Luo-Rudy d ynamic kinetics, and the results were qualitatively similar, including the higher threshold for regenerative repolarization compared to regenerative d epolarization. Conclusion: This characterization of the nonlinear response of isolated cel ls to transmembrane current, including phase resetting, should aid in under standing the mechanisms of defibrillation because shock-induced changes in V-m and APD have been implicated as important factors in determining defibr illation success.