Phenotypic Characterization of a Novel Long-QT Syndrome Mutation (R1623Q) in the Cardiac Sodium Channel

Abstract

The R1623Q mutation produces inactivation gating defects that differ mechanistically from those caused by LQT3 mutations. These findings provide a biophysical explanation for this severe long-QT phenotype and extend our understanding of the mechanistic role of the S4 segment in cardiac sodium channel inactivation gating and class I antiarrhythmic drug action.