title: Differential blocking action of dihydropyridine Ca2+ antagonists on a T-type Ca2+ channel (alpha1G) expressed in Xenopus oocytes.
abstract: 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, alpha1G, expressed in Xenopus oocytes. These effects were compared with those on T-type Ca2+ channel. Rabbit L-type (alpha1Calpha2/deltabeta1a) or rat T-type (alpha1G) Ca2+ channel was expressed in Xenopus oocytes by injection of cRNA for each subunit. The Ba 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 mibefradil were tested. Cilnidipine, felodipine, nifedipine, nilvadipine, minodipine, and nitrendipine had little effect on the T-type channel. The blocks by drugs at 10 microM 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 alpha1G channel subtype. The action of dihydropyridine Ca2+ antagonists in clinical treatment should be evaluated on the basis of subtype selectivity.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan. tfrkw@med.teikyo-u.ac.jp
authors.forename: Taiji
authors.initials: T
authors.lastname: Furukawa
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nukada
authors.forename: Reiko
authors.initials: R
authors.lastname: Miura
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ooga
authors.forename: Mituyoshi
authors.initials: M
authors.lastname: Honda
authors.forename: Suguru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koganesawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Isshiki
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D004095:Dihydropyridines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D014981:Xenopus
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D018075:RNA, Complementary