白细胞介素-2改变心肌细胞钙瞬态的频率依赖性

目的:观察白细胞介素-2(IL-2)对大鼠心肌细胞内钙处理能力的影响。方法:采用细胞内双波长钙荧光系统检测稳定状态及不同电刺激频率下单个心肌细胞钙瞬态的变化。结果:在稳定状态(0.2Hz)下, 2×10⁵U/LIL-2抑制心肌细胞钙瞬态的幅度和峰值, 使舒张末钙水平升高, 钙瞬态下降相时间常数延长。细胞外钙浓度为1.25mmol/L时, 心肌细胞舒张末钙水平、钙瞬态的幅度均随刺激频率(0.2-1.0Hz)的增高而增高。IL-2抑制了这种正性的频率依赖关系, 当将外钙浓度增加至2.5mmol/L时并不能改变其抑制作用。咖啡因诱导的内贮钙释放也呈现正性的频率依赖关系, 2×10⁵U/LIL-2抑制其频率依赖关系。在细胞外钙浓度为1.25mmol/L时, 两组间的钙瞬态机械恢复特性无差异, 当外钙为2.5mmol/L时, IL-2组的恢复率减慢。结论:IL-2通过抑制肌浆网内贮钙的释放而抑制了细胞内钙瞬态的正性频率依赖关系。

Interleukin-2 altered the frequency -dependent relationship of intracellular calcium in rat ventricular myocytes

AIM:We examined the effect of interleukin-2 (IL-2) on calcium handling of rat cardiomyocytes. METHODS:The effects of steady state and transient changes in stimulus frequency on the intracellular calcium transient were investigated in the isolated ventricular myocytes with spectrofluorometry technique. RESULTS: Under the steady state (0.2 Hz), IL-2 at 2×10⁵U/L decreased the peak [Ca²⁺] i and amplitude of the [Ca²⁺]i transient, increased the diastolic calcium level, and prolonged the decay of the calcium transient. At 1.25 mmol/L of extracellular [Ca²⁺], when increasing the stimulus frequency from 0.2 to 1.0 Hz, diastolic calcium level and peak [Ca²⁺] i as well as the amplitude of the transient were increased. The positive frequency relationship was blunted in the IL-2-treated myocytes and this was not normalized by increasing extracellular [Ca²⁺] to 2.5 mmol/L. The caffeine induced Ca²⁺ release was increased with increase in stimulus frequency. IL-2 inhibited the frequency relationship of caffeine induced Ca²⁺ release. The restitution was not different between control and IL-2 groups at the 1.25 mmol/L of extracellular [Ca²⁺], which was slowed in IL-2-treated myocytes when the extracellular [Ca²⁺] was increased to 2.5 mmol/L. CONCLUSIONS:It is concluded that the blunted frequency response of IL-2-treated myocytes was resulted from the decrease in SR Ca²⁺ release, which was related to depression of SR function. Despite the evidence of depressed SR Ca²⁺ uptake, the restitution of calcium transient at 1.25 mmol/L of extracellular remains unchanged, which maybe due to the increase in the Na⁺/Ca²⁺ exchanger activity.