Effect of cytoskeleton disruptors on L-type Ca channel distribution in rat ventricular myocytes
Effect of cytoskeleton disruptors on L-type Ca channel distribution in rat ventricular myocytes
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DOI：
10.1016/j.ceca.2005.07.006
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发表时间：
2005-11-01
期刊：
影响因子：
4
通讯作者：
Orchard, CH
中科院分区：
文献类型：
--
作者：
Leach, RN;Desai, JC;Orchard, CH
细胞骨架在心脏细胞功能的许多方面起着重要作用，包括蛋白质运输。然而，细胞骨架在心肌细胞钙通道定位中的作用尚不清楚。因此，在本研究中，我们研究了细胞骨架破坏剂细胞松弛素D，latrunculin，nocadazole和秋水仙碱对大鼠心室肌细胞培养96 h期间钙通道分布的影响。在培养过程中，在这些代理商的情况下，细胞边缘变圆，T-小管密度下降，和L-型钙通道的一个I（孔形成）亚基的正常横向分布变得更加点状和核周;这些变化与损失的同步钙释放响应电刺激。破坏微管蛋白使用nocadazole或秋水仙碱或螯合单体肌动蛋白latrunculin对这些变化没有影响。与此相反，细胞松弛素D抑制这些变化：细胞形状，t-小管密度，横向钙通道染色和同步钙释放在培养过程中保持。蛋白质合成抑制剂环己酰亚胺与细胞松弛素具有相似的作用。这些数据表明，细胞松弛素稳定肌动蛋白在成人心室肌细胞培养，从而稳定细胞的结构和功能，肌动蛋白是重要的运输L-型钙通道从核周区的t-小管，在那里他们通常位于和提供触发钙释放。(c)2005爱思唯尔有限公司保留所有权利。
The cytoskeleton plays an important role in many aspects of cardiac cell function, including protein trafficking. However, the role of the cytoskeleton in determining Ca channel location in cardiac myocytes is unknown. In the present study we therefore investigated the effect of the cytoskeletal disruptors cytochalasin D, latrunculin, nocadazole and colchicine on the distribution of Ca channels in rat ventricular myocytes during culture for up to 96 h. During culture in the absence of these agents, cell edges became rounded, t-tubule density decreased, and the normal transverse distribution of the a I (pore-forming) subunit of the L-type Ca channel became more punctate and peri-nuclear; these changes were associated with loss of synchronous Ca release in response to electrical stimulation. Disruption of tubulin using nocadazole or colchicine or sequestration of monomeric actin by latrunculin had no effect on these changes. In contrast, cytochalasin D inhibited these changes: cell shape, t-tubule density, transverse Ca channel staining and synchronous Ca release were maintained during culture. The protein synthesis inhibitor cycloheximide had similar effects to cytochalasin. These data suggest that cytochalasin stabilizes actin in adult ventricular myocytes in culture, thus stabilizing cell structure and function, and that actin is important in trafficking L-type Ca channels from the peri-nuclear region to the t-tubules, where they are normally located and provide the trigger for Ca release. (c) 2005 Elsevier Ltd. All rights reserved.