Mibefradil, an I-Ca,I-T blocker, effectively blocks I-Ca,I-L in rabbit sinus node cells

To test the hypothesis that the Ca2+ channel blocker mibefradil slows heart rate due to inhibition of T-type Ca2+ current in pacemaker cells, we studi ed effects of mibefradil on action potentials and ionic currents of isolate d rabbit sinus node cells using the patch clamp technique. Mibefradil (100 nM and 1 mu M) reduced spontaneous rate, decreased action potential amplitu de and finally stopped impulse initiation. This action was not due to the d rug effect on hyperpolarization-activated pacemaker current, but can be exp lained by attenuation of both T- and L-type Ca2+ currents, which were inhib ited by mibefradil almost equally (55% and 64% inhibition with 1 mu M for T - and L-types, respectively). (C) 2000 Elsevier Science B.V. All rights res erved.