Why the study?
Do class 1 anti-arrhythmic drugs selectively block persistent late Na+ currents compared to peak Na+ currents in HEK-293 cells expressing inactivation-deficient Na+ channels?
Do class 1 anti-arrhythmic drugs selectively block persistent late Na+ currents compared to peak Na+ currents in HEK-293 cells expressing inactivation-deficient Na+ channels?
Class 1 anti-arrhythmic drugs selectively block persistent late Na+ currents, supporting the hypothesis that these currents are in vivo targets at therapeutic concentrations.
After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293 cells 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 microM 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.
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Wang et al. (2004) studied this question.
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