Ca ²⁺ /Calmodulin-Dependent Protein Kinase II–Based Regulation of Voltage-Gated Na ⁺ Channel in Cardiac Disease

Abstract

We identify the mechanism for 2 human arrhythmia variants that affect Na(v)1.5 channel activity through direct effects on channel posttranslational modification. We propose that the CaMKII phosphorylation motif in the Na(v)1.5 DI-DII cytoplasmic loop is a critical nodal point for proarrhythmic changes to Na(v)1.5 in congenital and acquired cardiac disease.