Abstract
To further explore the role of interleukin-2 (IL-2) in cardiac function, we investigated its effects on the intracellular calcium transient and the activity of sarcoplasmic reticulum (SR) Ca2+-ATPase in rat cardiomyocytes. IL-2 (200 U/ml) decreased the amplitude of electrically stimulated and caffeine-induced intracellular Ca2+ transients in ventricular myocytes, but increased the end-diastolic calcium level. IL-2 did not affect the sarcolemmal L-type Ca2+ channel activity. The activity of SR Ca2+-ATPase from IL-2-treated hearts increased in a dose-dependent manner, but the sarcolemmal Ca2+-ATPase activity did not change. After incubation of SR with ATP, the activity of SR Ca2+-ATPase from IL-2-treated hearts increased much more than that in the control group. The responsiveness of SR Ca2+-ATPase from IL-2-perfused hearts to the free calcium concentration was inhibited. The Ca2+ uptake and Ca2+ content were reduced in the SR vesicles prepared from IL-2-treated rat heart. Pretreatment with the κ-opioid receptor antagonist nor-binaltorphimine (10 nM) attenuated the effect of IL-2 on the SR Ca2+-ATPase activity, SR Ca2+ uptake, and Ca2+ content. The activity of Ca2+-ATPase in SR isolated from untreated hearts did not change when IL-2 and SR were coincubated. Thus, we conclude that the decreased calcium transient induced by IL-2 results from reduced SR calcium release, which is due to decreased SR Ca2+ uptake mediated by cardiac κ-opioid receptors, but not from reduced activity of the sarcolemmal L-type calcium channel.
Footnotes
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This study was funded by Zhejiang Provincial Natural Science Foundation of China for Talent (RC99038).
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DOI: 10.1124/jpet.102.048264.
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ABBREVIATIONS: SR, sarcoplasmic reticulum; IL-2, interleukin-2; MOPS, 3-(N-morpholino)propanesulfonic acid; BSA, bovine serum albumin; AM, acetoxymethyl ester; K-H, Krebs-Henseleit; [Ca2+]i, intracellular calcium concentration; Pi, inorganic phosphate; nor-BNI, nor-binaltorphimine.
- Received December 17, 2002.
- Accepted April 28, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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