Actions of Mibefradil, Efonidipine and Nifedipine Block of Recombinant T- and L-Type Ca2+ Channels with Distinct Inhibitory Mechanisms

Abstract

We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca²⁺ channels expressed separately in mammalian cells. All these Ca²⁺ channel antagonists blocked T-type Ca²⁺ channel currents (I_Ca(T)) with distinct blocking manners: I_Ca(T) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC₅₀s of these Ca²⁺ channel antagonists to I_Ca(T) and L-type Ca²⁺ channel current (I_Ca(L)) were 1.2 µmol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 µmol/l for mibefradil, and 0.35 µmol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca²⁺ channel.