T-type Ca2+ channels and cardiac pacemaker activity

It is well known that T-type Ca(2+) channels differ from L-type Ca(2+) channels on the basis of their low-voltage activation range and rapid inactivation, and therefore can contribute to the pacemaker activity of sinoatrial node cells in the heart. However, proper elucidation of their function on the pacemaker activity has been hampered by the lack of selective pharmacology as well as cell-to-cell difference in the amplitude of T-type Ca(2+) current. In the present study, therefore, we investigated the effects of mibefradil, a selective T-type Ca(2+) channel blocker, on the spontaneous action potential of rabbit sinoatrial node cells. Mibefradil strongly inhibited the spontaneous action potential. In particular, suppression of the slow diastolic depolarization was more marked than that had been expected from a sole inhibition of T-type Ca(2+) channels. T-type Ca(2+) channels may be an important contributor to automaticity in heart cells. Alternatively, mibefradil might have blocked other current system (s) which serves as the main pacemaker current, and thereby inhibited the pacemaker activity.