The transient receptor potential Melastatin 4 (TRPM4) channel is a calcium-activated non-selective cation channel expressed widely. In the heart, using a knock-out mouse model, the TRPM4 channel has been shown to be involved in multiple processes, including β-adrenergic regulation, cardiac conduction, action potential duration and hypertrophic adaptations. This channel was recently shown to be involved in stress-induced cardiac arrhythmias in a mouse model overexpressing TRPM4 in ventricular cardiomyocytes. However, the link between TRPM4 channel expression in ventricular cardiomyocytes, the hypertrophic response to stress and/or cellular arrhythmias has yet to be elucidated. In this present study, we induced pathological hypertrophy in response to myocardial infarction using a mouse model of Trpm4 gene invalidation, and demonstrate that TRPM4 is essential for survival. We also demonstrate that the TRPM4 is required to activate both the Akt and Calcineurin pathways. Finally, using two hypertrophy models, either a physiological response to endurance training or a pathological response to myocardial infarction, we show that TRPM4 plays a role in regulating transient calcium amplitudes and leads to the development of cellular arrhythmias potentially in cooperation with the Sodium-calcium exchange (NCX).

Here, we report two functions of the TRPM4 channel: first its role in adaptive hypertrophy, and second its association with NCX could mediate transient calcium amplitudes which trigger cellular arrhythmias.

瞬时受体电位 Melastatin 4 (TRPM4) 通道是一种钙激活的非选择性阳离子通道，广泛表达。在心脏中，使用敲除小鼠模型，TRPM4 通道已被证明参与多个过程，包括 β-肾上腺素能调节、心脏传导、动作电位持续时间和肥大适应。最近显示该通道与在心室心肌细胞中过表达 TRPM4 的小鼠模型中的应激诱导的心律失常有关。然而，心室心肌细胞中 TRPM4 通道表达与应激和/或细胞心律失常的肥大反应之间的联系尚未阐明。在本研究中，我们使用Trpm4小鼠模型诱导病理性肥大以应对心肌梗塞基因失效，并证明 TRPM4 对生存至关重要。我们还证明 TRPM4 是激活 Akt 和钙调神经磷酸酶途径所必需的。最后，使用两种肥大模型，无论是对耐力训练的生理反应还是对心肌梗塞的病理反应，我们表明 TRPM4 在调节瞬时钙振幅方面发挥作用，并可能与钠-钙协同作用导致细胞心律失常的发展。交换（NCX）。

在这里，我们报告了 TRPM4 通道的两个功能：首先它在适应性肥大中的作用，其次它与 NCX 的关联可以介导触发细胞心律失常的瞬时钙振幅。