Mechanisms of atrial-selective block of Na⁺ channels by ranolazine: II. Insights from a mathematical model.

ABSTRACT: Block of Na(+) channel conductance by ranolazine displays marked atrial selectivity that is an order of magnitude higher that of other class I antiarrhythmic drugs. Here, we present a Markovian model of the Na(+) channel gating, which includes activation-inactivation coupling, aimed at elucidating the mechanisms underlying this potent atrial selectivity of ranolazine. The model incorporates experimentally observed differences between atrial and ventricular Na(+) channel gating, including a more negative position of the steady-state inactivation curve in atrial versus ventricular cells. The model assumes that ranolazine requires a hydrophilic access pathway to the channel binding site, which is modulated by both activation and inactivation gates of the channel. Kinetic rate constants were o

SUBMITTER: Nesterenko VV 

PROVIDER: S-EPMC3197376 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature