Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells

The effects of zinc (Zn²⁺) on ATP-evoked dopamine release was investigated in rat pheochromocytoma PC12 cells. Zn²⁺ potentiated the dopamine release evoked by 30 μM ATP in a concentration-dependent manner over a concentration range from 3 to 300 μM. High concentration of Zn²⁺ (>1 mM) inhibited the release. Zn²⁺ (10 μM) shifted the concentration-response curve of the ATP-evoked dopamine release to the left without affecting the maximal response. The dopamine release evoked by 40 mM KCl was not affected by Zn²⁺ (1-100 μM), whereas high concentration of Zn²⁺ (>300 μM) attenuated the response. The dopamine release evoked by 30 μM ATP in the presence of 10 μM Zn²⁺ were suppressed by suramin (30 μM), an antagonist to P₂-purinoceptors, to an extent similar to that in the absence of Zn²⁺. Zn²⁺ (1-100 μM) enhanced the ATP-evoked increase in intracellular Ca²⁺ concentration ([Ca]i) in the cells. The Ca²⁺ responses to ATP in the presence and absence of Zn²⁺ were abolished by external Ca²⁺-depletion. Under whole-cell voltage-clamp, Zn²⁺ (10 μM) augmented by two-fold the peak amplitude of an inward current evoked by 30 μM ATP. Taken together, it is suggested that Zn²⁺ enhances the ATP-evoked dopamine release by increasing sensitivity to ATP. The enhancement may be due to the augmentation of ATP-gated Ca²⁺-influx, but not due to modulation of cellular machinery downstream to [Ca]i rise. The enhancement of the ATP-mediated responses may underlie modulation by Zn²⁺ of physiological functions in various types of neuronal cells.