Abstract 13190: Integrin Linked Kinase is Required for Integrity of Cardiac Ion Current and Electrophysiologic Function

Introduction: The cardiac adaptor protein integrin-linked kinase (ILK) is a regulator of cardiac structure/function. This study investigated the ventricular cardiomyocyte ion channel/electrophysiological remodeling caused by cardiomyocyte-directed ILK deletion (ILK-KO) in mice. Methods: Mice expressing the mckCRE transgene and 2 loxP1-flanked ILK-alleles (ILK-KO) were compared to littermate controls (WT). Perforated and tight-seal patch clamp were used respectively to record action potentials (APs) and ion currents in isolate ventricular cardiomyocytes. Cardiac function was assessed by echocardiography and rhythms were recorded by 24 hr telemetry in conscious mice. Results: ILK-KO mice died suddenly (50% mortality at 8 wks and 100% mortality at 18 wks) with progressive dilated cardiomyopathy. Spontaneous ventricular tachyarrhythmias (VTs) were recorded in 60% (*P<0.001 vs WT) at 10 wks. At 5 wks, prior to cardiac dysfunction, ILK-KO increased action potential duration (APD) by 68%*. ICaL and IK1 were unch...