Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects.

ABSTRACT: Cardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD), either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. I_Ks (KCNQ1+KCNE1), a slowly activating K⁺ current, plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage-sensing domain (VSD) of the I_Ks channel. Here, we show that C28 specifically shifted I_Ks VSD activation in ventricle to more negative voltages and reversed the drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ven

SUBMITTER: Lin Y 

PROVIDER: S-EPMC8157969 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature