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

Abstract

To test the hypothesis that the Ca(2+) channel blocker mibefradil slows heart rate due to inhibition of T-type Ca(2+) current in pacemaker cells, we studied effects of mibefradil on action potentials and ionic currents of isolated rabbit sinus node cells using the patch clamp technique. Mibefradil (100 nM and 1 microM) reduced spontaneous rate, decreased action potential amplitude and finally stopped impulse initiation. This action was not due to the drug effect on hyperpolarization-activated pacemaker current, but can be explained by attenuation of both T- and L-type Ca(2+) currents, which were inhibited by mibefradil almost equally (55% and 64% inhibition with 1 microM for T- and L-types, respectively).