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

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...

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Bibliographic Details
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
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Summary: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
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1999.0989