Angiotensin II activates intermediate-conductance Ca2+ -activated K+ channels in arterial smooth muscle cells.
Angiotensin II activates intermediate-conductance Ca2+ -activated K+ channels in arterial smooth muscle cells.
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DOI：
10.1016/j.yjmcc.2006.07.010
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发表时间：
2006-12
影响因子：
5
通讯作者：
Y. Hayabuchi;Y. Nakaya;Sonoko Yasui;K. Mawatari;K. Mori;Mitsujiro Suzuki;S. Kagami
中科院分区：
文献类型：
--
作者：
Y. Hayabuchi;Y. Nakaya;Sonoko Yasui;K. Mawatari;K. Mori;Mitsujiro Suzuki;S. Kagami
血管紧张素II（Angiostensin II，Ang II）调节血管平滑肌细胞的迁移和增殖。最近的研究表明，中电导钙激活钾通道（IKca）在细胞迁移和增殖中起着重要作用。然而，尚不清楚Ang II的作用是否与IKca通道调节有关。在这里，我们研究了血管紧张素II在动脉平滑肌细胞IKca通道的调制。应用膜片钳技术研究了培养的胚胎大鼠主动脉平滑肌细胞（A10）中IKca通道的功能性表达。这些细胞主要表达IKca通道。与此相反，大电导钙激活的K+（BKca）电流很少观察到在切除的补丁。血管紧张素Ⅱ以收缩依赖的方式增加IKca电流。AT 1选择性拮抗剂Losartan（1.0 μM）可阻断Ang Ⅱ对IKca通道的激活。用100 μM肉豆蔻酰化蛋白激酶C抑制剂肽20-28或10 μM GF 109203 X预处理可完全阻断Ang II诱导的IKca电流激活，而在100 μM RP-环3′，5′-磷酸氢腺苷三乙铵（一种蛋白激酶A抑制剂）或1.0 μM KT-5823存在下，Ang II的作用不能被阻止，蛋白激酶G抑制剂。二酰基甘油的膜渗透类似物1，2-二辛酰基-sn-甘油（10 μM）诱导IKca电流激活。这些数据表明，Ang II通过激活蛋白激酶C激活IKca通道，并且AT 1受体参与这些通道的调节。
Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+-activated K+(IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+-activated K+(BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 μM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 μM myristoylated protein kinase C inhibitor peptide 20-28 or 10 μM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 μM Rp-cyclic 3′, 5′-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 μM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 μM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.