Interleukin-2 increases activity of sarcoplasmic reticulum Ca2+-ATPase, but decreases its sensitivity to calcium in rat cardiomyocytes.

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 kappa-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 kappa-opioid receptors, but not from reduced activity of the sarcolemmal L-type calcium channel.