PUFA stabilizes a conductive state of the selectivity filter in IKs channels.

ABSTRACT: In cardiomyocytes, the KCNQ1/KCNE1 channel complex mediates the slow delayed-rectifier current (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause long QT syndrome (LQTS), a syndrome with a prolonged QT interval on the ECG, which increases the risk of ventricular arrhythmia and sudden cardiac death. One potential therapeutical intervention for LQTS is based on targeting IKs channels to restore channel function and/or the physiological QT interval. Polyunsaturated fatty acids (PUFAs) are potent activators of KCNQ1 channels and activate IKs channels by binding to two different sites, one in the voltage sensor domain - which shifts the voltage dependence to more negative voltages - and the other in the pore domain - which increases the ma

SUBMITTER: Golluscio A 

PROVIDER: S-EPMC11527429 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature