Differential blocking action of dihydropyridine Ca2+ antagonists on a T-type Ca2+ channel (α1G) expressed in Xenopus oocytes

Recent reports show that efonidipine, a dihydropyridine Ca2+ antagonist, has blocking action on T-type Ca2+ channels, which may produce favorable actions on cardiovascular systems. However, the effects of other dihydropyridine Ca2+ antagonists on T-type Ca2+ 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 Ca2+ channel subtype, alpha(1G,) expressed in Xenopus oocytes. These effects were compared with those on T-type Ca2+ channel. Rabbit L-type (alpha(1c)alpha(2)/deltabeta(1A)) or rat T-type (alpha(1G)) Ca2+ channel was expressed in Xenopus oocytes by injection of cRNA for each subunit. The Ba2+ currents through expressed channels were measured by conventional 2-microelectrode voltage-clamp methods. Twelve DHPs (amlodipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine) and mibe-fradil were tested. Cilnidipine, felodipine, nifedipine, nilvadipine, minodipine, and nitrendipine had little effect on the T -type channel. The blocks by drugs at 10 muM 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 Ca2+ antagonists have blocking action on the a,G channel subtype. The action of dihydropyridine Ca2+ antagonists in clinical treatment should be evaluated on the basis of subtype selectivity.