TRPM4 channels in the cardiovascular system: Physiology, pathophysiology, and pharmacology
TRPM4 channels in the cardiovascular system: Physiology, pathophysiology, and pharmacology
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DOI：
10.1016/j.bcp.2012.06.021
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发表时间：
2012-10-01
影响因子：
5.8
通讯作者：
Rougier, Jean-Sebastien
中科院分区：
文献类型：
--
作者：
Abriel, Hugues;Syam, Ninda;Rougier, Jean-Sebastien
瞬时受体电位通道（TRP）家族在人类基因组中包含至少28个基因。这些通道在许多不同的组织中广泛表达，包括心血管系统的组织。瞬时受体电位通道melastatin 4（TRPM 4）是一种钙离子激活的非特异性阳离子通道，对钙离子是不可渗透的。TRPM4在心血管系统的许多细胞中表达，例如传导途径的心脏细胞和动脉和静脉平滑肌细胞。这篇综述文章总结了最近描述的TRPM4在正常生理和各种疾病状态的作用。人类基因TRPM4的遗传变异与几种心脏传导障碍有关。TRPM4也被认为在脊髓损伤后的继发性出血中起关键作用。自发性高血压大鼠心肌肥厚表现为心脏TRPM 4通道的过度表达。最近的研究表明，TRPM4在心血管生理和疾病中起着重要作用，即使大多数分子和细胞机制尚未阐明。我们总结这篇评论文章的简要概述的化合物，已被证明是抑制或激活TRPM4在实验条件下。基于最近的发现，TRPM4通道可以被提议作为心血管疾病（例如高血压和心律失常）的药物治疗的未来靶点。(C)2012 Elsevier Inc. All rights reserved.
The transient receptor potential channel (TRP) family comprises at least 28 genes in the human genome. These channels are widely expressed in many different tissues, including those of the cardiovascular system. The transient receptor potential channel melastatin 4 (TRPM4) is a Ca2+-activated non-specific cationic channel, which is impermeable to Ca2+. TRPM4 is expressed in many cells of the cardiovascular system, such as cardiac cells of the conduction pathway and arterial and venous smooth muscle cells. This review article summarizes the recently described roles of TRPM4 in normal physiology and in various disease states. Genetic variants in the human gene TRPM4 have been linked to several cardiac conduction disorders. TRPM4 has also been proposed to play a crucial role in secondary hemorrhage following spinal cord injuries. Spontaneously hypertensive rats with cardiac hypertrophy were shown to over-express the cardiac TRPM4 channel. Recent studies suggest that TRPM4 plays an important role in cardiovascular physiology and disease, even if most of the molecular and cellular mechanisms have yet to be elucidated. We conclude this review article with a brief overview of the compounds that have been shown to either inhibit or activate TRPM4 under experimental conditions. Based on recent findings, the TRPM4 channel can be proposed as a future target for the pharmacological treatment of cardiovascular disorders, such as hypertension and cardiac arrhythmias. (C) 2012 Elsevier Inc. All rights reserved.