Modulation of the cardiac sodium channel Na_V1.5 peak and late currents by NAD⁺ precursors.

ABSTRACT:

Rationale

The cardiac sodium channel Na_V1.5, encoded by SCN5A, produces the rapidly inactivating depolarizing current I_Na that is responsible for the initiation and propagation of the cardiac action potential. Acquired and inherited dysfunction of Na_V1.5 results in either decreased peak I_Na or increased residual late I_Na (I_Na,L), leading to tachy/bradyarrhythmias and sudden cardiac death. Previous studies have shown that increased cellular NAD⁺ and NAD⁺/NADH ratio increase I_Na through suppression of mitochondrial reactive oxygen species and PKC-mediated Na_V1.5 phosphorylation. In addition, NAD⁺-dependent deacetylation of Na_V1.5 at K1479 by Sirtuin 1 in

SUBMITTER: Matasic DS 

PROVIDER: S-EPMC7234910 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature