The Transient Receptor Potential Melastatin 4 (TRPM4) is a transmembrane N-glycosylated ion channel that belongs to the large family of TRP proteins. It has an equal permeability to Na⁺ and K⁺ and is activated via an increase of the intracellular calcium concentration and membrane depolarization. Due to its wide distribution, TRPM4 dysfunction has been linked with several pathophysiological processes, including inherited cardiac arrhythmias. Many pathogenic variants of the TRPM4 gene have been identified in patients with different forms of cardiac disorders such as conduction defects, Brugada syndrome, and congenital long QT syndrome. At the cellular level, these variants induce either gain- or loss-of-function of TRPM4 channels for similar clinical phenotypes. However, the molecular mechanisms associating these functional alterations to the clinical phenotypes remain poorly understood. The main objective of this article is to review the major cardiac TRPM4 channelopathies and recent advances regarding their genetic background and the underlying molecular mechanisms.

中文翻译：

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遗传性心律失常综合征：专注于TRPM4通道病背后的分子机制。

瞬态受体潜在Melastatin 4（TRPM4）是跨膜N-糖基化离子通道，属于TRP蛋白的大家族。它对Na ⁺和K ⁺具有相同的渗透性，并通过增加细胞内钙浓度和膜去极化来激活。由于其分布广泛，TRPM4功能障碍与多种病理生理过程有关，包括遗传性心律不齐。TRPM4的许多致病变异已经在患有各种形式的心脏疾病（例如传导缺陷，Brugada综合征和先天性长QT综合征）的患者中鉴定出该基因。在细胞水平上，这些变体诱导相似临床表型的TRPM4通道功能获得或丧失。但是，将这些功能改变与临床表型相关联的分子机制仍然知之甚少。本文的主要目的是回顾主要的心脏TRPM4通道病变以及有关其遗传背景和潜在分子机制的最新进展。