Differential Blocking Action of Dihydropyridine Ca2+ Antagonists on a T-Type Ca2+ Channel (α1G) Expressed in Xenopus Oocytes
Differential Blocking Action of Dihydropyridine Ca2+ Antagonists on a T-Type Ca2+ Channel (α1G) Expressed in Xenopus Oocytes
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DOI：
10.1097/01.fjc.0000154374.88283.15
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发表时间：
2005-03
影响因子：
3
通讯作者：
T. Furukawa;T. Nukada;R. Miura;Kyoji Ooga;M. Honda;Suguru Watanabe;Satoshi Koganesawa;T. Isshiki
中科院分区：
文献类型：
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作者：
T. Furukawa;T. Nukada;R. Miura;Kyoji Ooga;M. Honda;Suguru Watanabe;Satoshi Koganesawa;T. Isshiki
近年来的研究表明，二氢吡啶类钙拮抗剂依福地平（efonidipine）对T型钙通道具有阻断作用，可能对心血管系统产生有利的作用。然而，其他二氢吡啶类钙拮抗剂对T-型钙通道的作用尚未研究。因此，在这项研究中，我们研究了临床上用于治疗高血压的二氢吡啶化合物对爪蟾卵母细胞中表达的T型钙通道亚型α1G的影响。并与对T型钙通道的作用进行了比较。兔L型（α1Cα2/δβ1a）或大鼠T型（α1G）钙通道通过注射各亚基的cRNA在爪蟾卵母细胞中表达。用常规的双微电极电压钳方法测量通过表达通道的Ba 2+电流。检测了12种DHP（氯地平、巴尼地平、贝尼地平、西尼地平、依福地平、非洛地平、马尼地平、尼卡地平、硝苯地平、尼伐地平、尼莫地平、尼群地平）和米贝拉地尔。西尼地平、非洛地平、硝苯地平、尼伐地平、米诺地平和尼群地平对T-型通道的作用不大。在-100 mV的保持电位下，10 μM药物的阻断率小于10%。其余6种药物对T型通道的阻断作用与L型通道相当。阻断作用也与米贝拉地尔相当。这些结果表明，许多二氢吡啶类钙拮抗剂对α1G通道亚型具有阻断作用。二氢吡啶类钙拮抗剂在临床治疗中的作用应根据亚型选择性进行评价。
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, α1G, expressed in Xenopus oocytes. These effects were compared with those on T-type Ca2+ channel. Rabbit L-type (α1Cα2/δβ1a) or rat T-type (α1G) 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 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 Ca2+ antagonists have blocking action on the α1G channel subtype. The action of dihydropyridine Ca2+ antagonists in clinical treatment should be evaluated on the basis of subtype selectivity.