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

To elicit the correlation between the adrenergic transmitter release and calmodulin (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 norepinephrine, the concentration of free Ca2+ in rat synaptosome was increased by verapamil 10, 50, and 100 mumol.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.