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- W1543340050 abstract "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%*. I CaL and I K1 were unchanged, but fast inactivating transient outward (I to,f ) and slowly inactivating delayed rectifier (I K,slow ) K currents were reduced by 40%* and 34%* respectively. At 10 wks, LV systolic, diastolic dimensions increased by 72%*, 31%* respectively and LVEF decreased by 42%*; I CaL , I K1 , I to,f and I K,slow were all significantly decreased (by 23%, 32%, 38%, 53% respectively). APD was increased by 114%* and EADs/triggered activity were recorded. To assess mechanisms of specific K + current interactions, ILK was immunoprecitated (IPed) from cardiomyocyte membranes and K + channel subunits detected by immunoblot (Figure). Kv4.2 co-IPed with ILK, indicating direct physical interaction; whereas Kv1.4, Kv4.3 and KChIP2 did not. Conclusions: Cardiomyocyte ILK-deletion causes dilated cardiomyopathy, extensive ionic remodeling, VT and sudden death. Early K + current changes and co-IP point to a specific interaction with Kv4.2 subunits in pathogenesis." @default.
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- W1543340050 date "2014-11-25" @default.
- W1543340050 modified "2023-10-02" @default.
- W1543340050 title "Abstract 13190: Integrin Linked Kinase is Required for Integrity of Cardiac Ion Current and Electrophysiologic Function" @default.
- W1543340050 doi "https://doi.org/10.1161/circ.130.suppl_2.13190" @default.
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