维拉帕米对大鼠脑突触体内Ca^(2+)和Ca^((2+))Mg^((2+))-ATP酶的影响

Effect of verapamil on Ca2+ and Ca(1+) Mg(2+)-ATPase activity in rat brain synaptosomes

维拉帕米(Ver)10,50和100μmol·L^(-1)能增加高K^+和去甲肾上腺素(NE)所致大鼠脑突触体内游离Ca^(2+)的浓度,但使静息状态突触体内游离Ca^(2+)浓度下降。Ver还抑制突触体Ca^((2+))Mg^((2+))-ATP酶活性。结果提示:与静息状态不同,在神经末梢受到刺激时,Ver可能是通过抑制CaM,进而抑制Ca^((2+))Mg^((2+))-ATP酶活性,使胞浆内游离Ca^((2+))升高,引起递质释放量增加。

To elicit the correlation between the adrenergic transmitter release and calmod-ulin (CaM), the effect of verapamil on the free Ca2+ concentration was measured with fluorescence analysis and Ca(2+) Mg(2+)-ATPase activity in rat synaptosomes were studied. When stimulated with high-K+ or nore-pinephrine, the concentration of free Ca2+ in rat synaptosome was increased by verapamil 10, 50, and 100 μmol·L-1. But the free Ca2+ concentration in the resting synaptosome was reduced by verapamil. The activity of Ca(2+) Mg(2+)-ATPase in synaptosome was remarkably inhibited by verapamil in a dose -dependent manner. These results support our hypothesis that CaM not only acts directly on the vesicles to enhance the transmitter release, but also acts on the activity of Ca(2+) Mg(2+)-ATPase to reduce the free Ca2+ in the cytosol, and indirectly inhibited the transmitter release.