Cellular Basis for the Acute Inhibitory Effects of IL-6 and TNF- α on Excitation-contraction Coupling

• Published in: Journal of molecular and cellular cardiology 1999-08, Vol.31 (8), p.1457-1467
• Main Authors: Sugishita, Kazuro, Kinugawa, Koh-ichiro, Shimizu, Tatsuya, Harada, Kazumasa, Matsui, Hiroshi, Takahashi, Toshiyuki, Serizawa, Takashi, Kohmoto, Osami
• Format: Article
• Language: English
• Subjects: [Ca2+]itransients; Animals; Calcium - physiology; Calcium Channels - physiology; Calcium current; Female; Guinea Pigs; Guinea-pig heart; Heart Ventricles - drug effects; Interleukin-6; Interleukin-6 - pharmacology; Myocardial Contraction - drug effects; Negative inotropism; Nitric oxide; Nitric Oxide - physiology; Patch-Clamp Techniques; Sphingosine; Sphingosine - metabolism; Sphingosine - pharmacology; Tumor necrosis factor- α; Tumor Necrosis Factor-alpha - pharmacology; Ventricular Function
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1999.0989

There is controversy over whether nitric oxide (NO) mediates acute negative inotropic actions of cytokines including tumor necrosis factor-alpha (TNF- α). The reports from established laboratories have appeared inconsistent, which could be due to species differences. Thus, we tried to elucidate the mechanisms underlying negative inotropic actions of interleukin-6 (IL-6) and TNF- α in the same model. We studied the effects of cytokines on [Ca2+]itransients (using indo-1), cell shortening (CS) (using a video motion detector) and thel -type Ca2+channel current (ICa) (using the whole cell perforated patch clamp technique) in isolated guinea-pig ventricular myocytes. IL-6 (1000 U/ml) or TNF- α (500 U/ml) decreased both peak systolic [Ca2+]i(IL-6: 0.43±0.01 to 0.40±0.01, n=5, P