Gating Properties of Mutant Sodium Channels and Responses to Sodium Current Inhibitors Predict Mexiletine-Sensitive Mutations of Long QT Syndrome 3

Abstract

The N1325S, R1623Q, and M1652R mutations are associated with a variable augmentation of late <i>I</i> _Na, which was reversed by MEX. M1652R mutation changes the conformation of Na_v1.5 that disrupt the inactivation of channel affecting MEX binding, corresponding to the poor response to MEX. The lidocaine test, molecular modeling, and drugs screening in cells expressing mutant channels are useful for predicting the effectiveness of late <i>I</i> _Na inhibitors.