Yamaguchi Yohei, Iribe Gentaro, Kaneko Toshiyuki, Takahashi Ken, Numaga-Tomita Takuro, Nishida Motohiro, Birnbaumer Lutz, Naruse Keiji
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
Department of Physiology, Asahikawa Medical University, Asahikawa, Hokkaido, 078-8510, Japan.
J Physiol Sci. 2018 Mar;68(2):153-164. doi: 10.1007/s12576-016-0519-3. Epub 2017 Jan 19.
When a cardiac muscle is held in a stretched position, its [Ca] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca concentration ([Ca]) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch. An AT1R blocker, a phospholipase C inhibitor, and a TRPC3 inhibitor suppressed the SSC. These inhibitors also abolished the observed SSC-like slow increase in [Ca] induced by angiotensin II, instead of stretch. Furthermore, the SSC was not observed in TRPC3 knockout mice. Simulation and immunohistochemical studies suggest that sarcolemmal TRPC3 is responsible for the SSC. These results indicate that sarcolemmal TRPC3, regulated by AT1R, causes the SSC.
当心肌处于拉伸状态时，其[Ca]瞬变在几分钟内缓慢增加，这一过程被称为应激诱导的细胞内钙浓度（[Ca]）缓慢增加（SSC）。瞬时受体电位香草酸亚型3（TRPC3）形成一种受1型血管紧张素II受体（AT1R）调节的非选择性阳离子通道。在本研究中，我们研究了TRPC3在SSC中的作用。分离的小鼠心室肌细胞受到电刺激并持续拉伸。一种AT1R阻滞剂、一种磷脂酶C抑制剂和一种TRPC3抑制剂抑制了SSC。这些抑制剂还消除了由血管紧张素II而非拉伸诱导的观察到的类似SSC的[Ca]缓慢增加。此外，在TRPC3基因敲除小鼠中未观察到SSC。模拟和免疫组化研究表明，肌膜TRPC3是SSC的原因。这些结果表明，受AT1R调节的肌膜TRPC3导致了SSC。
