Tumor necrosis factor- downregulates the voltage gated outward K+ current in cultured neonatal rat cardiomyocytes: A possible cause of electrical remodeling in diseased hearts

Abstract

Background: Inflammatory cytokines have been reported to contribute to the progression of cardiac remodeling in various heart diseases and a remarkable prolongation of the monophasic action potential duration and reductions in the expression of Kv4.2 and K+ channel-interacting protein-2 (KChIP-2) in a rat autoimmune myocarditis model have been documented. In this study, the effect of tumor necrosis factor- (TNF-) on cultured cardiomyocytes was evaluated, focusing on the change in the voltage-gated outward K+ current and expression of related molecules. Methods and Results: Cardiomyocytes isolated from 1-day-old Lewis rats were cultured for 72 h and treated with TNF- (50 ng/ml) for an additional 48 h. The myocytes treated with TNF- showed a 22% reduction in the peak K+ current, which consisted of a transient outward K+ current (Ito) and 1.4-fold enhancement of the cell-capacitance in comparison with the control. Among the cardiac ion channel related molecules evaluated in this study, Kv4.2 and KChIP-2 mRNA exhibited remarkable reductions (p<0.05). Conclusions: Treatment with TNF- induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF- might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.