Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel.

ABSTRACT: The voltage-gated cardiac Na⁺ channel (Na_v1.5), encoded by the SCN5A gene, conducts the inward depolarizing cardiac Na⁺ current (I_Na) and is vital for normal cardiac electrical activity. Inherited loss-of-function mutations in SCN5A lead to defects in the generation and conduction of the cardiac electrical impulse and are associated with various arrhythmia phenotypes. Here we show that sirtuin 1 deacetylase (Sirt1) deacetylates Na_v1.5 at lysine 1479 (K1479) and stimulates I_Na via lysine-deacetylation-mediated trafficking of Na_v1.5 to the plasma membrane. Cardiac Sirt1 deficiency in mice induces hyperacetylation of K1479 in Na_v1.5, decreases expression of Na_v1.5 on the cardiomyocyte membrane,

SUBMITTER: Vikram A 

PROVIDER: S-EPMC6218171 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature