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

• Published in: Circulation Journal Vol. 70; no. 5; pp. 605 - 609
• Main Authors: Kawada, Hideaki, Niwano, Shinichi, Niwano, Hiroe, Yumoto, Yoshihiro, Wakisaka, Yuko, Yuge, Masaru, Kawahara, Katsumasa, Izumi, Tohru
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 01.05.2006
• Subjects: Action Potentials; Animals; Animals, Newborn; Cardiac remodeling; Cardiomyocytes; Cells, Cultured; Disease Models, Animal; Down-Regulation - drug effects; Down-Regulation - genetics; Heart Diseases - pathology; Heart Diseases - physiopathology; Hypertrophy - chemically induced; Hypertrophy - pathology; Kv Channel-Interacting Proteins - drug effects; Kv Channel-Interacting Proteins - genetics; Kv4.2; Myocarditis - immunology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neonatal rats; Potassium - metabolism; Potassium Channels, Voltage-Gated - drug effects; Potassium Channels, Voltage-Gated - genetics; Rats; Rats, Inbred Lew; RNA, Messenger - analysis; Shal Potassium Channels - drug effects; Shal Potassium Channels - genetics; TNF-α; Transient outward K+ current; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.605

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 72 h and treated with TNF-α (50 ng/ml) for an additional 48 h. 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 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-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. (Circ J 2006; 70: 605 - 609)