Differential blocking action of dihydropyridine Ca2+ antagonists on a T-type Ca2+ channel (alpha1G) expressed in Xenopus oocytes.

Recent reports show that efonidipine, a dihydropyridine Ca 2 + antagonist, has blocking action on T-type Ca 2 + channels, which may produce favorable actions on cardiovascular systems. However, the effects of other dihydropyridine Ca 2 + antagonists on T-type Ca 2 + channels have not been investigated yet. Therefore, in this study, we examined the effects of dihydropyridine compounds clinically used for treatment of hypertension on a T-type Ca 2 + channel subtype, α 1 G , expressed in Xenopus oocytes. These effects were compared with those on T-type Ca 2 + channel. Rabbit L-type (α 1 C α 2 /δβ 1 a ) or rat T-type (α 1 G ) Ca 2 + channel was expressed in Xenopus oocytes by injection of cRNA for each subunit. The Ba 2 + currents through expressed channels were measured by conventional 2-microelectrode voltage-clamp methods. Twelve DHPs (amlodipine, bamidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine) and mibefradil were tested. Cilnidipine, felodipine, nifedipine, nilvadipine, minodipine, and nitrendipine had little effect on the T-type channel. The blocks by drugs at 10 μM were less than 10% at a holding potential of -100 mV. The remaining 6 drugs had blocking action on the T-type channel comparable to that on the L-type channel. The blocking actions were also comparable to that by mibefradil. These results show that many dihydropyridine Ca 2 + antagonists have blocking action on the α 1 G channel subtype. The action of dihydropyridine Ca 2 + antagonists in clinical treatment should be evaluated on the basis of subtype selectivity.