The role of L-type calcium current (I_Ca,L) in impulse generation was studied in single sinoatrial nodal myocytes of the rabbit, with the use of the amphotericin-perforated patch-clamp technique. Nifedipine, at a concentration of 5 µM, was used to block I_Ca,L. At this concentration, nifedipine selectively blocked I_Ca,L for 81% without affecting the T-type calcium current (I_Ca,T), the fast sodium current, the delayed rectifier current (I_K), and the hyperpolarization-activated inward current. Furthermore, we did not observe the sustained inward current. The selective action of nifedipine on I_Ca,L enabled us to determine the activation threshold of I_Ca,L, which was around 60 mV. As nifedipine (5 µM) abolished spontaneous activity, we used a combined voltage- and current-clamp protocol to study the effects of I_Ca,L blockade on repolarization and diastolic depolarization. This protocol mimics the action potential such that the repolarization and subsequent diastolic depolarization are studied in current-clamp conditions. Nifedipine significantly decreased action potential duration at 50% repolarization and reduced diastolic depolarization rate over the entire diastole. Evidence was found that recovery from inactivation of I_Ca,L occurs during repolarization, which makes I_Ca,L available already early in diastole. We conclude that I_Ca,L contributes significantly to the net inward current during diastole and can modulate the entire diastolic depolarization.

nifedipine; delayed rectifier current; hyperpolarization-activated current; T-type calcium current; fast sodium current; sustained inward current

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