Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.
Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.
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心脏疤痕组织中的成纤维细胞直接调节心脏兴奋性和心律失常发生。
DOI：
10.1126/science.adh9925
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Song,Zh
中科院分区：
文献类型：
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作者：
Wang,Yijie;Li,Qihao;Tao,Bo;Angelini,Marina;Ramadoss,Sivakumar;Sun,Baiming;Wang,Ping;Krokhaleva,Yuliya;Ma,Feiyang;Gu,Yiqian;Espinoza,Alejandro;Yamauchi,Ken;Pellegrini,Matteo;Novitch,Bennett;Olcese,Riccardo;Qu,Zhilin;Song,Zh
心脏损伤后，死亡的心肌被疤痕组织取代。成纤维细胞可以与肌细胞电耦合，成纤维细胞膜电位的变化可以导致肌细胞兴奋性，这表明疤痕组织中的成纤维细胞-肌细胞耦合可能是心律失常发生的原因。然而，肌细胞和成纤维细胞电耦合的生理相关性及其对体内心脏兴奋性的影响尚未得到证实。我们对小鼠进行了基因改造，使其仅在心脏成纤维细胞中表达光遗传学阳离子通道 ChR2 (H134R)。心肌梗塞后，疤痕组织的光刺激引起器官范围的心脏兴奋并诱发这些动物的心律失常。通过实验方法补充计算模型，我们发现间隙连接和触觉耦合以协同但功能冗余的方式兴奋与成纤维细胞耦合的肌细胞。
After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.