Ahmad Azmi A, Streiff Molly, Hunter Chris, Hu Qinghua, Sachse Frank B
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, USA; Bioengineering Department, University of Utah, Salt Lake City, USA.
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, USA.
Prog Biophys Mol Biol. 2017 Nov;130(Pt B):254-263. doi: 10.1016/j.pbiomolbio.2017.06.005. Epub 2017 Jun 16.
Transient receptor potential canonical (TRPC) channels constitute a family of seven Ca permeable ion channels, named TRPC1 to 7. These channels are abundantly expressed in the mammalian heart, yet mechanisms underlying activation of TRPC channels and their precise role in cardiac physiology remain poorly understood. In this review, we perused original literature regarding TRPC channels in cardiomyocytes. We first reviewed studies on TRPC channel assembly and sub-cellular localization across multiple species and cell types. Our review indicates that TRPC localization in cardiac cells is still a topic of controversy. We then examined common molecular biology tools used to infer on location and physiological roles of TRPC channels in the heart. We subsequently reviewed pharmacological tools used to modulate TRPC activity in both cardiac and non-cardiac cells. Suggested physiological roles in the heart include modulation of heart rate and sensing of mechanical strain. We examined studies on the contribution of TRPC to cardiac pathophysiology, mainly hypertrophic signaling. Several TRPC channels, particularly TRPC1, 3 and 6 were proposed to play a crucial role in hypertrophic signaling. Finally, we discussed gaps in our understanding of the location and physiological role of TRPC channels in cardiomyocytes. Closing these gaps will be crucial to gain a full understanding of the role of TRPC channels in cardiac pathophysiology and to further explore these channels as targets for treatments for cardiac diseases, in particular, hypertrophy.
瞬时受体电位香草酸亚型（TRPC）通道构成了一个由七个钙离子通透离子通道组成的家族，命名为TRPC1至TRPC7。这些通道在哺乳动物心脏中大量表达，然而TRPC通道的激活机制及其在心脏生理学中的精确作用仍知之甚少。在本综述中，我们研读了有关心肌细胞中TRPC通道的原始文献。我们首先回顾了跨多种物种和细胞类型的TRPC通道组装和亚细胞定位的研究。我们的综述表明，TRPC在心脏细胞中的定位仍然是一个有争议的话题。然后，我们研究了用于推断TRPC通道在心脏中的位置和生理作用的常见分子生物学工具。随后，我们回顾了用于调节心脏和非心脏细胞中TRPC活性的药理学工具。在心脏中推测的生理作用包括心率调节和机械应变感知。我们研究了TRPC对心脏病理生理学，主要是肥大信号传导贡献的研究。几个TRPC通道，特别是TRPC1、3和6，被认为在肥大信号传导中起关键作用。最后，我们讨论了我们对心肌细胞中TRPC通道的位置和生理作用理解上的差距。填补这些差距对于全面了解TRPC通道在心脏病理生理学中的作用以及进一步探索这些通道作为心脏病，特别是肥大治疗靶点至关重要。
