EA 4650, Signalisation, Electrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, GIP Cyceron, Université de Caen Normandie, CHU de Caen, 14032 Caen, France.
Cells. 2021 Mar 12;10(3):636. doi: 10.3390/cells10030636.
Aldosterone plays a major role in atrial structural and electrical remodeling, in particular through Ca-transient perturbations and shortening of the action potential. The Ca-activated non-selective cation channel Transient Receptor Potential Melastatin 4 (TRPM4) participates in atrial action potential. The aim of our study was to elucidate the interactions between aldosterone and TRPM4 in atrial remodeling and arrhythmias susceptibility. Hyperaldosteronemia, combined with a high salt diet, was induced in mice by subcutaneously implanted osmotic pumps during 4 weeks, delivering aldosterone or physiological serum for control animals. The experiments were conducted in wild type animals () as well as knock-out animals (). The atrial diameter measured by echocardiography was higher in compared to animals, and hyperaldosteronemia-salt produced a dilatation in both groups. Action potentials duration and triggered arrhythmias were measured using intracellular microelectrodes on the isolated left atrium. Hyperaldosteronemia-salt prolong action potential in mice but had no effect on mice. In the control group (no aldosterone-salt treatment), no triggered arrythmias were recorded in mice, but a high level was detected in mice. Hyperaldosteronemia-salt enhanced the occurrence of arrhythmias (early as well as delayed-afterdepolarization) in mice but decreased it in animals. Atrial connexin43 immunolabelling indicated their disorganization at the intercalated disks and a redistribution at the lateral side induced by hyperaldosteronemia-salt but also by disruption. In addition, hyperaldosteronemia-salt produced pronounced atrial endothelial thickening in both groups. Altogether, our results indicated that hyperaldosteronemia-salt and TRPM4 participate in atrial electrical and structural remodeling. It appears that TRPM4 is involved in aldosterone-induced atrial action potential shortening. In addition, TRPM4 may promote aldosterone-induced atrial arrhythmias, however, the underlying mechanisms remain to be explored.
醛固酮在心房结构和电重构中起主要作用，特别是通过钙瞬变扰动和动作电位缩短。钙激活的非选择性阳离子通道瞬时受体电位 melastatin 4（TRPM4）参与了心房动作电位。我们的研究目的是阐明醛固酮和 TRPM4 在心房重构和心律失常易感性中的相互作用。通过皮下植入渗透泵在 4 周内向小鼠中诱导高醛固酮血症，同时给予醛固酮或生理血清作为对照动物。实验在野生型动物（）以及 敲除动物（）中进行。超声心动图测量的心房直径在 中高于 动物，并且高醛固酮血症-盐在两组中均产生扩张。使用分离的左心房上的细胞内微电极测量动作电位持续时间和触发心律失常。高醛固酮血症-盐延长了 小鼠的动作电位，但对 小鼠没有影响。在对照组（无醛固酮-盐处理）中，在 小鼠中未记录到触发性心律失常，但在 小鼠中检测到高水平。高醛固酮血症-盐增强了 小鼠心律失常（早期和延迟后除极）的发生，但降低了 动物的心律失常。心房连接蛋白 43 的免疫标记表明其在闰盘处的排列紊乱，以及由高醛固酮血症-盐引起的侧向重新分布，但也由 破坏引起。此外，高醛固酮血症-盐在两组中均导致明显的心房内皮增厚。总之，我们的结果表明，高醛固酮血症-盐和 TRPM4 参与了心房的电重构和结构重构。似乎 TRPM4 参与了醛固酮诱导的心房动作电位缩短。此外，TRPM4 可能促进醛固酮诱导的心房心律失常，但潜在机制仍有待探索。
