Actin cytoskeletal modulation of pressure-induced depolarization and Ca2+ influx in cerebral arteries
Actin cytoskeletal modulation of pressure-induced depolarization and Ca2+ influx in cerebral arteries
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DOI：
10.1152/ajpheart.00441.2001
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发表时间：
2002-04-01
影响因子：
4.8
通讯作者：
Osol, G
中科院分区：
文献类型：
--
作者：
Gokina, NI;Osol, G
本研究的目的是检查肌动蛋白细胞骨架在压力诱导的膜去极化和脑动脉肌源性收缩背后的 Ca2+ 流入的发展中的作用。将管腔内压力从 10 mmHg 升高至 60 mmHg 会诱导膜去极化，增加细胞内胞质 Ca2+ 浓度 ([Ca2+](i))，并在完整和裸露的大鼠大脑后动脉中引起肌源性收缩。用细胞松弛素 D (5 μM) 或 latrunculin A (3 μM) 预处理消除了收缩，但增强了 [Ca2+](i) 反应；类似地，对有张力的血管或在存在 60 mM K+ 的情况下对血管进行急性应用细胞松弛素 D，会引起松弛并伴有 [Ca2+](i) 的增加。硝苯地平 (3 muM) 抑制细胞松弛素 D 的作用，表明肌动蛋白细胞骨架破坏会增加 Ca2+ 通过电压敏感的 L 型 Ca2+ 通道的流入。最后，压力诱导的去极化在细胞松弛素 D 的存在下得到增强，进一步证实了肌动蛋白细胞骨架在离子通道功能调节中的作用。总之，这些结果表明血管平滑肌肌动蛋白细胞骨架动力学通过对膜电位的影响以及对 L 型 Ca2+ 通道的直接影响来控制脑动脉直径。
The objective of this study was to examine the role of the actin cytoskeleton in the development of pressure-induced membrane depolarization and Ca2+ influx underlying myogenic constriction in cerebral arteries. Elevating intraluminal pressure from 10 to 60 mmHg induced membrane depolarization, increased intracellular cytosolic Ca2+ concentration ([Ca2+](i)) and elicited myogenic constriction in both intact and denuded rat posterior cerebral arteries. Pretreatment with cytochalasin D (5 muM) or latrunculin A (3 muM) abolished constriction but enhanced the [Ca2+](i) response; similarly, acute application of cytochalasin D to vessels with tone, or in the presence of 60 mM K+, elicited relaxation accompanied by an increase in [Ca2+](i). The effects of cytochalasin D were inhibited by nifedipine (3 muM), demonstrating that actin cytoskeletal disruption augments Ca2+ influx through voltage-sensitive L-type Ca2+ channels. Finally, pressure-induced depolarization was enhanced in the presence of cytochalasin D, further substantiating a role for the actin cytoskeleton in the modulation of ion channel function. Together, these results implicate vascular smooth muscle actin cytoskeletal dynamics in the control of cerebral artery diameter through their influence on membrane potential as well as via a direct effect on L-type Ca2+ channels.