TY - JOUR T1 - Interleukin-2 Increases Activity of Sarcoplasmic Reticulum Ca<sup>2</sup><sup>+</sup>-ATPase, but Decreases Its Sensitivity to Calcium in Rat Cardiomyocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 572 LP - 580 DO - 10.1124/jpet.102.048264 VL - 306 IS - 2 AU - Chun-Mei Cao AU - Qiang Xia AU - Iain C. Bruce AU - Xiong Zhang AU - Chen Fu AU - Jun-Zhu Chen Y1 - 2003/08/01 UR - http://jpet.aspetjournals.org/content/306/2/572.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -