PubMed 16636498

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.2

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

Authors: Hideaki Kawada, Shinichi Niwano, Hiroe Niwano, Yoshihiro Yumoto, Yuko Wakisaka, Masaru Yuge, Katsumasa Kawahara, Tohru Izumi

Journal, date & volume: Circ. J., 2006 May , 70, 605-9

PubMed link:

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-alpha (TNF-alpha) on cultured cardiomyocytes was evaluated, focusing on the change in the voltage-gated outward K+ current and expression of related molecules.Cardiomyocytes isolated from 1-day-old Lewis rats were cultured for 72 h and treated with TNF-alpha (50 ng/ml) for an additional 48 h. The myocytes treated with TNF-alpha 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).Treatment with TNF-alpha induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF-alpha might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.