Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes

Abstract

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca2+ handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca2+ transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca2+ transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca2+ concentration ([Ca 2+]o), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca2+ level and peak intracellular Ca 2+ concentration ([Ca2+]i), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca2+]i transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca2+]i transient was not normalized by increasing [Ca2+]o to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca2+ release. Blockade of sarcoplasmic reticulum (SR) Ca2+-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca2+]o, which was slowed in IL-2-treated myocytes when [Ca2+]o was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca 2+]o. The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na+-Ca2+ exchange activity, but not to any change in L-type Ca2+ channels. © 2003 Elsevier Ltd. All rights reserved.