Cardiac melanocytes influence atrial reactive oxygen species involved with electrical and structural remodeling in mice

Cardiac melanocyte‐like cells ( CMLC s) contribute to atrial arrhythmias when missing the melanin synthesis enzyme dopachrome tautomerase (Dct). While scavenging reactive oxygen species ( ROS ) in Dct‐null mice partially suppressed atrial arrhythmias, it remains unclear if CMLC s influence atrial ROS and structure or if the electrical response of CMLC s to ROS differs from that of atrial myocytes. This study is designed to determine if CMLC s contribute to overall atrial oxidative stress or structural remodeling, and if ROS affects the electrophysiology of CMLC s differently than atrial myocytes. Immunohistochemical analysis showed higher expression of the oxidative marker 8‐hydroxy‐2′‐deoxyguanosine in Dct‐null atria versus Dct‐heterozygous (Dct‐het) atria. Exposing isolated CMLC s from Dct‐het and Dct‐null mice to hydrogen peroxide increased superoxide anion more in Dct‐null CMLC s. Trichrome staining showed increased fibrosis in Dct‐null atria, and treating Dct‐null mice with the ROS scavenger Tempol reduced atrial fibrosis. Action potential recordings from atrial myocytes and isolated Dct‐het and Dct‐null CMLC s in response to hydrogen peroxide showed that the EC 50 for action potential duration ( APD ) prolongation of Dct‐null CMLC s was 8.2 ± 1.7 μmol/L versus 16.8 ± 2.0 μmol/L for Dct‐het CMLC s, 19.9 ± 2.1 μmol/L for Dct‐null atrial myocytes, and 20.5 ± 1.9 μmol/L for Dct‐het atrial myocytes. However, APD 90 was longer in CMLC s versus atrial myocytes in response to hydrogen peroxide. Hydrogen peroxide also induced more afterdepolarizations in CMLC s compared to atrial myocytes. These studies suggest that Dct within CMLC s contributes to atrial ROS balance and remodeling. ROS prolongs APD to a greater extent and induces afterdepolarizations more frequently in CMLC s than in atrial myocytes.