Mibefradil, an I(Ca,T) blocker, effectively blocks I(Ca,L) in rabbit sinus node cells.
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).
Department of Pharmacology, Columbia University, 630 W. 168th St., 10032, New York, NY, USA. 1p141@columbia.edu
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Protas
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Robinson
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D005260:Female; D020748:Mibefradil / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D020748:Mibefradil; C038806:1,4-dihydropyridine; D009543:Nifedipine