Abstract 106: Kcne2 Gene Deletion Predisposes To Sudden Cardiac Death

Abstract

Sudden cardiac death (SCD) accounts for an estimated 1000 deaths per day in the United States alone. SCD typically involves an ischemic substrate and culminates in a lethal ventricular arrhythmia. KCNE2 potassium channel subunit gene variants are associated with cardiac arrhythmias including Long QT Syndrome, and impaired cardiac potassium channel function. KCNE2 is expressed in ventricular and atrial myocytes, but is also present in various epithelia, the potential cardiac implications of which have been largely overlooked. Here, we investigated whether KCNE2 gene disruption could also perturb cardiac function via disruption of extracardiac roles. Targeted Kcne2 deletion in mice caused hypercholesterolemia, glucose dysregulation and anemia - factors all known to predispose to myocardial ischemia in later life. In addition, Kcne2 -/- mice exhibited hyperkalemia, elevated serum angiotensin II, and prolonged T wave elevation - all potentially arrhythmogenic. Finally, in young female mice lacking overt baseline ischemia, Kcne2 -/- but not Kcne2 +/+ mice exhibited polymorphic ventricular tachycardia, ventricular fibrillation and SCD within 20 minutes of reperfusion after brief coronary artery ligation. The findings demonstrate that Kcne2 disruption creates a spectrum of abnormalities that produce both systemic and electrical substrates for SCD.