Ionic mechanisms of the cardiac pacemaker potential.

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The ionic mechanisms of the cardiac pacemaker action potential were studied by the patch clamp technique applied to dissociated sinoatrial node myocytes of rabbit heart. (1) The hyperpolarization-activated current was shown to be carried by monovalent cations, such as Na^+ and K^+. The current was found to be blocked by Sr in a time-and voltage-dependent manner. The current activation required Cl^- in the external solution. Varying concentrations of K^+ affected the apparent selectivity of the channels. The time-course of deactivation on depolarization was found to be dependent on the variety in the monovalent cation concentrations. A mathematical model was developed to estimate the contribution of the current to the diastolic depolarization, which was around 1-4pA.(2) We found a new inward current which is activated over the diastolic potential range. The pharmacological properties were similar to those of the L-type Ca channel, but the ion selectivity was different. Namely the current was carried by Na^+. The current was increased by the beta-adrenergic stimulation, and is consistent with the idea that this sustained inward current takes a major role in driving the diastolic depolarization.