Laboratory of Ion Channel Research, VIB Centre for Brain and Disease Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
J Physiol. 2024 Apr;602(8):1605-1621. doi: 10.1113/JP283831. Epub 2023 May 14.
Cardiac arrhythmias pose a major threat to a patient's health, yet prove to be often difficult to predict, prevent and treat. A key mechanism in the occurrence of arrhythmias is disturbed Ca homeostasis in cardiac muscle cells. As a Ca-activated non-selective cation channel, TRPM4 has been linked to Ca-induced arrhythmias, potentially contributing to translating an increase in intracellular Ca concentration into membrane depolarisation and an increase in cellular excitability. Indeed, evidence from genetically modified mice, analysis of mutations in human patients and the identification of a TRPM4 blocking compound that can be applied in vivo further underscore this hypothesis. Here, we provide an overview of these data in the context of our current understanding of Ca-dependent arrhythmias.
心律失常对患者的健康构成重大威胁，但往往难以预测、预防和治疗。心律失常发生的一个关键机制是心肌细胞中钙稳态的紊乱。作为一种 Ca 激活的非选择性阳离子通道，TRPM4 与 Ca 诱导的心律失常有关，可能将细胞内 Ca 浓度的增加转化为膜去极化和细胞兴奋性的增加。事实上，来自基因修饰小鼠的证据、对人类患者突变的分析以及鉴定出一种可在体内应用的 TRPM4 阻断化合物进一步证实了这一假说。在这里，我们根据我们目前对 Ca 依赖性心律失常的理解，概述了这些数据。
