Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action.

ABSTRACT: 1 We studied the effects of ranolazine, an antianginal agent with promise as an antiarrhythmic drug, on wild-type (WT) and long QT syndrome variant 3 (LQT-3) mutant Na(+) channels expressed in human embryonic kidney (HEK) 293 cells and knock-in mouse cardiomyocytes and used site-directed mutagenesis to probe the site of action of the drug. 2 We find preferential ranolazine block of sustained vs peak Na(+) channel current for LQT-3 mutant (DeltaKPQ and Y1795C) channels (IC(50)=15 vs 135 microM) with similar results obtained in HEK 293 cells and knock-in myocytes. 3 Ranolazine block of both peak and sustained Na(+) channel current is significantly reduced by mutation (F1760A) of a single residue previously shown to contribute critically to the binding site for local anesthetic (LA) molecules

SUBMITTER: Fredj S 

PROVIDER: S-EPMC1617037 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature