Tumor Necrosis Factor-α Downregulates the Voltage Gated Outward K^+ Current in Cultured Neonatal Rat Cardiomyocytes : A Possible Cause of Electrical Remodeling in Diseased Hearts(EXPERIMENTAL INVESTIGATION)

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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-α (TNF-α) 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 72h and treated with TNF-α (50ng/ml) for an additional 48h. The myocytes treated with TNF-α 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 cellcapacitance 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-α induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF-α might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.
社団法人日本循環器学会の論文
2006-04-20