Inactivation-deficient human skeletal muscle Na+ channels (hNav1.4-L443C/A444W) in stably transfected HEK-293 cells.

After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293cells exhibited large inactivation-deficient Na+ currents. We subsequently established a stable cell line expressing robust inactivation-deficient Na+ currents. Persistent late Na+ currents were far more sensitive to block by class 1 anti-arrhythmic flecainide, mexiletine, propafenone, and amiodarone at 10 mu M than peak Na+ currents. Such results support a hypothesis that persistent late Na+ currents are in vivo targets for class 1 anti-arrhythmic drugs at their therapeutic plasma concentrations. Stably transfected HEK-293 cells expressing robust inactivation-deficient Na+ currents will likely be suitable for screening novel drugs that target persistent late Na+ currents selectively.