Cardiac macrophages facilitate electrical conduction through the atrioventricular-node (AV) in mice. A possible role for cardiomyocyte-macrophage coupling on the effect of antiarrhythmic therapy has not been investigated yet. Holter monitoring was conducted in LysM^CrexCsf1r^LsL−DTR mice (MM^DTR) under baseline conditions and after an elctrophysiological stress test by flecainide. In vivo effects were recapitulated in vitro by patch-clamp experiments. The underlying mechanism was characterized by expression and localization analysis of connexin43 (Cx43) and voltage-gated-sodium-channel-5 (Na_v1.5). ECG monitoring in MM^DTR mice did not show any significant conduction abnormalities but a significantly attenuated flecainide-induced extension of RR- and PP-intervals. Patch-clamp analysis revealed that the application of flecainide to neonatal rat ventricular cardiomyocytes (CMs) changed their resting-membrane-potential (RMP) to more negative potentials and decreased action-potential-duration (APD50). Coupling of macrophages to CMs significantly enhances the effects of flecainide, with a further reduction of the RMP and APD50, mediated by an upregulation of Cx43 and Na_v1.5 surface expression. Macrophage depletion in mice does not correlate with cardiac electric conduction delay. Cardiac macrophages amplify the effects of flecainide on electrophysiological properties of cardiomyocytes in vivo and in vitro. Mechanistically, formation of macrophage-cardiomyocyte cell–cell-contacts via Cx43 facilitates the recruitment of Na_v1.5 to the cell membrane increasing flecainide effects.

心脏巨噬细胞促进小鼠通过房室结 （AV） 的电传导。心肌细胞-巨噬细胞偶联对抗心律失常治疗效果的可能作用尚未得到研究。在基线条件下和氟卡尼电生理应激测试后，对 LysM^CrexCsf1r^LsL-DTR 小鼠 （MM^DTR） 进行动态心电图监测。通过膜片钳实验在体外概括体内效应。通过连接蛋白 43 （Cx43） 和电压门控钠通道-5 （Na_v1.5） 的表达和定位分析来表征其潜在机制。MM^DTR 小鼠的心电图监测未显示任何明显的传导异常，但氟卡尼诱导的 RR 和 PP 间期延长显着减弱。膜片钳分析显示，氟卡尼应用于新生大鼠心室心肌细胞 （CMs） 使其静息膜电位 （RMP） 变为更多的负电位，并降低动作电位持续时间 （APD50）。巨噬细胞与 CMs 的偶联显着增强了氟卡尼的作用，进一步降低 RMP 和 APD50，这是由 Cx43 和 Na_v1.5 表面表达的上调介导的。小鼠巨噬细胞耗竭与心脏电传导延迟无关。心脏巨噬细胞在体内和体外放大氟卡尼对心肌细胞电生理特性的影响 机制上，通过 Cx43 形成巨噬细胞-心肌细胞-细胞-接触，促进 Na_v1.5 募集到细胞膜，增加氟卡尼作用。