Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation.

ABSTRACT: Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration. In contrast, blocking palmitoylation increases closed-state channel inactivation and reduces myocyte excitability. We identify four cysteines as possible Nav1.5 palmitoylation substrates. A mutation of one of these is associated with cardiac arrhyt

SUBMITTER: Pei Z 

PROVIDER: S-EPMC4931030 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature