TRPV2 is critical for the maintenance of cardiac structure and function in mice.
TRPV2 is critical for the maintenance of cardiac structure and function in mice.
复制标题
DOI：
10.1038/ncomms4932
复制
发表时间：
2014-05-29
影响因子：
16.6
通讯作者：
Naruse, Keiji
中科院分区：
文献类型：
--
作者：
Katanosaka, Yuki;Iwasaki, Keiichiro;Ujihara, Yoshihiro;Takatsu, Satomi;Nishitsuji, Koki;Kanagawa, Motoi;Sudo, Atsushi;Toda, Tatsushi;Katanosaka, Kimiaki;Mohri, Satoshi;Naruse, Keiji
心脏对血流动力学应激具有动态代偿机制。然而，机械力如何在心脏中传导的分子细节尚不清楚。在这里，我们证明瞬时受体电位、2 型香草酸家族 (TRPV2) 阳离子通道对于维持心脏结构和功能至关重要。从成年小鼠心脏中消除 TRPV2 后 4 天内，心脏功能严重下降，支持与邻近心肌细胞机械耦合的闰盘解体，并出现心肌传导缺陷。 9 天后，TRPV2 缺陷心脏中单个肌细胞的细胞缩短和 Ca2+ 处理能力受到损害。 TRPV2 缺陷的新生儿心肌细胞不形成闰盘，并且没有表现出细胞外 Ca2+ 依赖性细胞内 Ca2+ 增加和响应拉伸刺激的胰岛素样生长因子 (IGF-1) 分泌。我们进一步证明，在 TRPV2 缺陷的心脏中，IGF-1 受体/PI3K/Akt 通路信号显着下调，并且 IGF-1 给药部分防止这些心脏中的心室扩张和心泵功能受损。我们的结果提高了我们对维持心脏结构和功能的分子过程的理解。 TRPV2 钙通道可通过机械拉伸激活，并可充当组织中的机械感受器。在这里，作者耗尽了成年小鼠心脏中的 TRPV2 钙通道，表明 TRPV2 对于维持心脏结构和功能很重要。
The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. The TRPV2 calcium channel can be activated by mechanical stretch and may act as a mechanoreceptor in tissues. Here the authors deplete the TRPV2 calcium channel from the hearts of adult mice, showing that TRPV2 is important for the maintenance of cardiac structure and function.
登录
查看更多内容
影响因子：
64.5
作者：
Cao P;Maximov A;Südhof TC
通讯作者：
Südhof TC
DOI：
10.1523/jneurosci.1384-09.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Park U;Vastani N;Guan Y;Raja SN;Koltzenburg M;Caterina MJ
通讯作者：
Caterina MJ
影响因子：
20.1
作者：
Guo, Danny;Kassiri, Zamaneh;Oudit, Gavin Y.
通讯作者：
Oudit, Gavin Y.
影响因子：
20.1
作者：
Muraki, K;Iwata, Y;Imaizumi, Y
通讯作者：
Imaizumi, Y
DOI：
10.1073/pnas.1203007109
发表时间：
2012-06-19
影响因子：
11.1
作者：
McCain, Megan L.;Lee, Hyungsuk;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit