Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.

ABSTRACT: Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K_2P potassium channel TREK-1 in a cAMP-dependent manner. POPDC1 and POPDC2 variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in Xenopus oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.5. POPDC proteins downregulate Nav1.5 currents in a cAMP-dependent manner by reducing the surface expression of the channel. POPDC2 and Nav1.5 are both expressed in different regions of the murine heart and consistently POPDC2 co-immunoprecipitates with Nav1.5 from native cardiac tissue. Strikingly, the knock-down of

SUBMITTER: Rinne S 

PROVIDER: S-EPMC11059135 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature