SELECTIVE-INHIBITION OF T-TYPE CA2+ CHANNELS BY RO-40-5967
SELECTIVE-INHIBITION OF T-TYPE CA2+ CHANNELS BY RO-40-5967
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DOI：
10.1161/01.res.75.1.144
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发表时间：
1994-07-01
影响因子：
20.1
通讯作者：
HERMSMEYER, K
中科院分区：
文献类型：
--
作者：
MISHRA, SK;HERMSMEYER, K
目前的研究表明，化学上新颖的非二氢吡啶Ca2+拮抗剂Ro 40-5967可以阻断血管肌肉细胞中的t型二价离子电流。在1 ~ 10 μ mol/L的Ro 40-5967浓度下，t型Ca2+通道被选择性地完全阻断，而L型Ca2+电流仅被阻断25% ~ 70%。将Ro 40-5967与选择性l型Ca2+通道的二氢吡啶类药物尼索地平结合使用，可以完全阻断所有Ca2+电流；因此，Ro 40-5967是第一个Ca2+通道阻滞剂，以消除治疗有用浓度的二氢吡啶不敏感电压依赖性Ca2+电流。在本研究中展示的T型和l型Ca2+电流的逐步顺序阻断满足了两种Ca2+通道类型独立身份的功能标准，并引入了一种药理学工具，有望在探索T型Ca2+通道功能中发挥重要作用。
The present study shows that the chemically novel nondihydropyridine Ca2+ antagonist, Ro 40-5967, blocks T-type divalent ion currents in vascular muscle cells. T-type Ca2+ channels were blocked selectively and completely by therapeutic concentrations of 1 to 10 mu mol/L Ro 40-5967, at which there was only 25% to 70% block of L-type Ca2+ currents. Using the combination of Ro 40-5967 and nisoldipine, a dihydropyridine selective for L-type Ca2+ channels, we found that all Ca2+ current could be completely blocked; thus, Ro 40-5967 is the first Ca2+ channel blocker to eliminate dihydropyridine-insensitive voltage-dependent Ca2+ current at therapeutically useful concentrations. The stepwise sequential block of T- and L-type Ca2+ currents demonstrated in the present study fulfills the functional criterion for the separate identity of the two Ca2+ channel types, and introduces a pharmacological tool that promises to be important in the exploration of T-type Ca2+ channel function.