Use-dependent block of Ca2+ current by moricizine in guinea-pig ventricular myocytes: a possible ionic mechanism of action potential shortening.

1. Whole cell patch clamp techniques were used to study the effects of moricizine on membrane currents in guinea-pig ventricular myocytes. 2. Application of moricizine caused reversible depression of the time-dependent outward K+ current. 3. The Na+/Ca2+ exchange current was not directly affected by moricizine. 4. Although moricizine hardly affected the L-type Ca2+ current when cells were stimulated at a frequency of 0.1 Hz, it suppressed the current at depolarized holding potentials in a use-dependent manner at 1 Hz. 5. Developments of use-dependent block of the Ca2+ current in the presence of moricizine were best expressed by two exponentials. Binding to both activated and inactivated states of the Ca2+ channel were supported from the binding kinetics study. 6. We concluded that moricizine suppressed the L-type Ca2+ current in a use-dependent manner and this might explain, at least in part, action potential shortening by the drug.