Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

摘要: Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias relief pain. To gain mechanistic insights into action anti-arrhythmics, we characterized biophysical properties Nav1.5 Nav1.7 channels stably expressed in HEK293 cells compared their use-dependent block response mexiletine using whole-cell patch clamp recordings. While the voltage-dependent activation or was not affected lidocaine, steady-state fast slow inactivation were significantly shifted hyperpolarized direction either dose-dependent manner. Both enhanced component closed-state inactivation, with exerting stronger inhibition on Nav1.7. The recovery from prolonged lidocaine. Furthermore, displayed a pronounced prominent than but channels. Taken together, our findings demonstrate differential responses blockade preferentially affect gating Nav1.5, as Nav1.7; exhibits Nav1.5. may help explain drug effectiveness advance new designs safe specific channel blockers cardiac arrhythmia