PO-01-241 ROLE OF THE TWO-PORE K CHANNEL TREK1 IN REGULATING HEART FAILURE-INDUCED VENTRICULAR ARRHYTHMIA

Despite therapeutic advances, heart failure (HF) remains a leading cause of death in the United States and is growing prevalence. Although disease-induced defects ion channel excitability expression put patients at higher risk for life-threatening ventricular arrhythmias, exact mechanisms by which HF leads to proarrhythmic dysfunction are not completely understood. Notably, several recent studies have identified important roles two-pore background K+ TREK1 regulating sinus rhythm, atrial arrhythmia, excitability. In present study, we examined putative role promoting failure-induced arrhythmia. We subjected wild type (WT) mice with cardiac-specific deficiency (TREK1cKO) transaortic constriction (TAC) surgery as model or sham procedure. Over course 6-12 weeks following surgery, structural electrical remodeling via echocardiography subsurface ECGs. At end time course, cells were isolated used patch clamp, Ca2+/contractility imaging, immunostaining. A subset hearts optical voltage mapping. observed that TREK1cKO experienced greater reductions cardiac function earlier development pressure overload compared WT mice, was maintained throughout course. Additionally, exhibited changes ECG parameters over including action potential duration (APD) prolongation, QTc QRS widening. However, TREK1cKOs also faster conduction, lower APD heterogeneity, arrhythmia inducibility 6 post-surgery. Overall, these results demonstrate potentially complex excitability, dynamics, susceptibility context overload-induced failure.