Toro L, Amador M, Stefani E
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Am J Physiol. 1990 Mar;258(3 Pt 2):H912-5. doi: 10.1152/ajpheart.1990.258.3.H912.
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 (congruent to 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 (congruent to 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.
血管紧张素II（ANG II）是冠状动脉血管和其他平滑肌的强效血管收缩剂。ANG II的作用之一是抑制钾离子电流，这可能导致去极化和收缩。因此，我们在单通道水平上研究了ANG II对钾离子通道调节的作用。我们研究了其对整合到脂质双分子层中的冠状动脉平滑肌钙激活钾（KCa）通道（约250 pS）的影响。在-20至-70 mV的电压和6.5至4的pCa条件下，KCa通道对外源性ANG II敏感。剂量反应曲线给出的半抑制浓度（Ki1/2）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数值。此外，出现了一种新的慢得多（约1秒）的关闭或“阻断”状态。我们得出结论，ANG II导致冠状动脉血管收缩的机制之一是直接抑制KCa通道，这有助于去极化和收缩。
