Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study.

ABSTRACT: Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state pref

SUBMITTER: Karoly R 

PROVIDER: S-EPMC2887460 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature