Block of T-type calcium channel by dihydropyridine calcium antagonists

Abstract

We examined the blocking action of 12 dihydropyridine Ca 2+ antagonist (amlodipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine) on the T-type Ca 2+ channel expressed in Xenopus oocytes. T-type Ca 2+ channel (α 1G subunit) or L-type Ca 2+ channel (α 1Cα 2β 2a) was expressed in Xenopus oocytes by cRNA injection. Blocking actions of the drugs were measured as blocking of membrane current through the expressed channel. The conventional two microelectrode voltage clamp method was used. Amlodipine, barnidipine, benidipine, efonidipine, manidipine and nicardipine had the blocking action of the T-type channel comparable to those on the L-type channel. Inhibition of the T-type channel by efonidipine and manidipine was greater than that of the L-type channel under our experimental conditions. Voltage dependence of the T-type channel block by the drugs varied. We showed that some dihydropyridine Ca 2+ antagonists have a T-type channel blocking action.