In Silico Assessment of Efficacy and Safety of IKur Inhibitors in Chronic Atrial Fibrillation: Role of Kinetics and State-Dependence of Drug Binding.

ABSTRACT: Current pharmacological therapy against atrial fibrillation (AF), the most common cardiac arrhythmia, is limited by moderate efficacy and adverse side effects including ventricular proarrhythmia and organ toxicity. One way to circumvent the former is to target ion channels that are predominantly expressed in atria vs. ventricles, such as KV1.5, carrying the ultra-rapid delayed-rectifier K+ current (IKur). Recently, we used an in silico strategy to define optimal KV1.5-targeting drug characteristics, including kinetics and state-dependent binding, that maximize AF-selectivity in human atrial cardiomyocytes in normal sinus rhythm (nSR). However, because of evidence for IKur being strongly diminished in long-standing persistent (chronic) AF (cAF), the therapeutic potential of drugs targeting

SUBMITTER: Ellinwood N 

PROVIDER: S-EPMC5681918 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature