C-terminal phosphorylation of Na_V1.5 impairs FGF13-dependent regulation of channel inactivation.

ABSTRACT: Voltage-gated Na⁺ (Na_V) channels are key regulators of myocardial excitability, and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in Na_V1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of Na_V1.5 subunits associated with these arrhythmogenic disorders and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the Na_V1.5 proteins purified from adult WT and failing CaMKIIδ_c-overexpressing (CaMKIIδ_c-Tg) mouse ventricles. Of 19 native Na_V1.5 phosphorylation

SUBMITTER: Burel S 

PROVIDER: S-EPMC5655519 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature