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-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.
Wang
S-Y
SY
Department of Biology, State University of New York at Albany, Albany, NY, USA. wang@zeus.bwh.harvard.edu
Moczydlowski
E
E
Wang
G
G
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001496:Batrachotoxins / Q000378:metabolism; D004594:Electrophysiology; D005424:Flecainide / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D062553:NAV1.4 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000889:Anti-Arrhythmia Agents; D001496:Batrachotoxins; D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels; D008801:Mexiletine; D012964:Sodium; D005424:Flecainide