Key result
Human L-type calcium current decays monotonically during rectangular pulses or endocardial action potentials, but becomes double-peaked during epicardial action potentials.
In human ventricular myocytes, L-type calcium channels can reopen during phase-1 repolarization of epicardial action potentials, contributing to the formation of the action potential dome.
May inform models of epicardial repolarization; leaves open clinical relevance to human arrhythmias.
AIMS: Present study was performed to compare the dynamics of human L-type calcium current (ICa,L) flowing during rectangular voltage pulses, voltage ramps, and action potentials (APs) recorded from epicardiac and endocardiac canine ventricular cells. METHODS: ICa,L was recorded in single myocytes isolated from undiseased human hearts using the whole cell voltage clamp technique. RESULTS: The decay of ICa,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 ICa,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 ICa,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: ICa,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.
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Fülöp et al. (2004) studied Undiseased human hearts. Epicardial action potentials and voltage ramps vs. Rectangular voltage pulses and endocardial action potentials was evaluated on Dynamics of human L-type calcium current (ICa,L). Human L-type calcium current decays monotonically during rectangular pulses or endocardial action potentials, but becomes double-peaked during epicardial action potentials.
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