The cardiomyopathy of Duchenne muscular dystrophy (DMD) is an important cause of morbidity and mortality in affected males with this dreaded muscle disease. Previous studies have implicated changes in expression and subcellular localization of connexin-43 (Cx43), the major ventricular gap junction protein, in DMD cardiomyopathy. In this issue of the JCI, Himelman et al. explore how hypophosphorylation of Cx43 at a triplet of serine residues (S325/S328/S330) in the regulatory C-terminus contributes to multiple features of the cardiomyopathy phenotype. Using a mouse model of DMD cardiomyopathy in which phosphomimetic glutamic acids are substituted for serines at these residues in Cx43, Himelman et al. observed reduced gap junction remodeling and lateralization of Cx43 immunosignals, protection against isoproterenol-induced arrhythmias, and improved Ca2+ homeostasis. This study contributes to the understanding of pathologic Cx43 remodeling and encourages further research into developing strategic interventions to mitigate cardiac dysfunction and arrhythmias in DMD patients.

中文翻译：

---

连接蛋白43在Duchenne肌营养不良性心肌病中的作用。

杜兴氏肌营养不良症（DMD）的心肌病是患有这种可怕肌肉疾病的受影响男性的发病率和死亡率的重要原因。先前的研究表明，DMD心肌病中主要的心室间隙连接蛋白连接蛋白43（Cx43）的表达和亚细胞定位发生变化。在JCI的这一期中，Himelman等人。探索在调节性C末端的三联体丝氨酸残基（S325 / S328 / S330）处Cx43的磷酸化不足如何导致心肌病表型的多个特征。Himelman等人使用DMD心肌病的小鼠模型，其中在Cx43的这些残基上用模拟磷酸谷氨酸替代了丝氨酸。观察到减少的缝隙连接重塑和Cx43免疫信号的侧向化，防止异丙肾上腺素引起的心律不齐，并改善了Ca2 +稳态。这项研究有助于了解病理Cx43重塑，并鼓励进一步研究开发可减轻DMD患者心脏功能障碍和心律不齐的策略性干预措施。