ANG-II INHIBITS CALCIUM-ACTIVATED POTASSIUM CHANNELS FROM CORONARY SMOOTH-MUSCLE IN LIPID BILAYERS
ANG-II INHIBITS CALCIUM-ACTIVATED POTASSIUM CHANNELS FROM CORONARY SMOOTH-MUSCLE IN LIPID BILAYERS
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DOI：
10.1152/ajpheart.1990.258.3.h912
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发表时间：
1990-03-01
影响因子：
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通讯作者：
STEFANI, E
中科院分区：
文献类型：
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作者：
TORO, L;AMADOR, M;STEFANI, E
血管紧张素II（Angiotensin II，ANG II）是一种强有力的血管收缩剂，可收缩冠状动脉和其他平滑肌。ANG II的作用之一是抑制K+电流，可能有助于去极化和收缩。因此，我们在单通道水平上研究了ANG II对K+通道的调节作用。我们研究了其对来自冠状动脉平滑肌的钙激活钾（KCa）通道（约250 pS）掺入脂质双层的作用。KCa通道对外部施加ANG II敏感，电压为-20至-70 mV，pCa为6.5至4。剂量-反应曲线给出的半抑制浓度（Ki 1/2）为58 nM，希尔系数为2.2，表明该过程中至少有两个位点。ANG II改变了通道的开放和关闭状态，影响了它们的比例和值。此外，出现了新的慢得多的（约1秒）关闭或“阻塞”状态。我们的结论是，血管紧张素II引起冠状动脉血管收缩的机制之一是直接抑制KCa通道的去极化和收缩。
Angiotensin II (ANG II) is a powerful vasoconstrictor of coronary vessels and other smooth muscles. One of the actions of ANG II is the inhibition of K+ currents, possibly contributing to depolarization and contraction. Therefore, we investigated the role of ANG II on the regulation of K+ channels at the single-channel level. We studied its effect on calcium-activated potassium (KCa) channels (.simeq.250 pS) from coronary smooth muscle incorporated into lipid bilayers. KCa channels were sensitive to externally applied ANG II at voltages from -20 to -70 mV and pCa between 6.5 and 4. The dose-response curve gave a concentration of half-inhibition (Ki1/2) of 58 nM and a Hill coefficient of 2.2, indicating a minimum of two sites in the process. ANG II modified the open and closed states of the channel, affecting their proportions and their values. In addition, a new much slower (.simeq.1 s) closed or "blocked" state appeared. We conclude that one of the mechanisms by which ANG II causes vasoconstriction of the coronary vessels is a direct inhibition of KCa channels contributing to depolarization and contraction.