Ankyrin-G Mediates Targeting of both Na+ and KATP Channels to the Cardiac Intercalated Disc

Abstract

Na+ channels and KATP channels are both enriched at the intercalated disk (ICD) of cardiomyocytes. Targeting of Na+ channels to the ICD is relatively well described. A Brugada-associated mutation in Nav1.5 has revealed a key role for Ankyrin G (AnkG). Here, we investigate whether a relationship exists between Na+ and KATP channel expression and targeting mechanisms to the ICD. We found that Na+ and KATP channels reciprocally negatively regulate each other's surface density. Physiological relevance is demonstrated since adenoviral delivery of Kir6.2 into cardiomyocytes reduces native INa.