Reopening of L-type calcium channels in human ventricular myocytes during applied epicardial action potentials

Aims: Present study was performed to compare the dynamics of human L-type calcium current (I-Ca,I-L) flowing during rectangular voltage pulses, voltage ramps, and action potentials (APs) recorded from epicardiac and endocardiac canine ventricular cells. Methods: I-Ca,I-L was recorded in single myocytes isolated from undiseased human hearts using the whole cell voltage clamp technique. Results: The decay of I-Ca,I-L was monotonic when using rectangular pulses or endocardial APs as voltage commands, whereas the current became double-peaked (displaying a second rise and fall) during epicardial (EPI) APs or voltage ramps used to mimic EPI APs. These I-Ca,I-L profiles were associated with single-hooked and double-hooked phase-plane trajectories, respectively. No sustained current was observed during the AP commands. Kinetics of deactivation and recovery from inactivation of human I-Ca,I-L were determined using twin-pulse voltage protocols and voltage ramps, and the results were similar to those obtained previously in canine cells under identical experimental conditions. Conclusions: I-Ca,I-L can inactivate partially before and deactivate during the phase-1 repolarization of the epicardiac AP, and reopening of these channels seems to be associated with formation of the dome.