Electrophysiological Functions of Macrophages are Involved in Atrial Fibrillation

Aim. I nflammation, in which macrophages play an important role as immune cells, is closely related to atrial fibrillation (AF). Recent studies have shown that macrophages participate electrical conduction in the heart, thus indicating that they have electrophysiological characteristics. However, whether the electrophysiology of macrophages is associated with AF or not remained unknown. Thus, we investigated the biological function changes in macrophages using patch-clamping after tachypacing to mimic AF. Material and methods . Atrial myocytes and macrophages were cultured. RNA sequencing was performed to investigate the expression change of atrial myocytes after tachypacing. Patch-clamping was conducted to measure the change of APD and ICa,L in macrophages after tachypacing. Rapid atrial stimulation was performed to measure the AF incidence in macrophage-specific CX43 knockout mice. Results. After tachypacing, the time required for 90% repolarization of the action potential and the ICa,L were reduced in macrophages. Furthermore, we found that tachypacing atrial myocytes led to the secretion of Wnt 7a, further inhibiting the expression of CACNA1C in macrophages. Moreover, the knockout of CX43 in macrophages decreased the incidence of AF in a mouse model of chronic inflammation. Conclusion. The electrophysiology of macrophages is related to the development of AF and might be a potential therapeutic target for AF therapy. Prospects for the transfer of laboratory data to the clinic: 1) Regulation of macrophage electrophysiology might be a potential therapeutic target for atrial fibrillation (AF). 2) A Wnt 7a inhibitor could be used to decrease AF incidence. 3) Blocking the interaction between macrophages and atrial myocytes might be a potential therapeutic target for AF.