Zn2+ potentiates excitatory action of ATP on mammalian neurons.

Despite the increasing recognition that ATP is an important extracellular excitatory mediator in the nervous system, the regulation of ATP receptors is poorly understood. Because the extracellular Zn2+ concentration is regulated in a variety of biological tissues, we studied modulation of the ATP-gated cation channel by Zn2+ in mammalian neurons using the whole-cell patch-clamp technique. In approximately 73% of cells tested, the amplitude of ATP-activated membrane ion current increased up to 5-fold in the presence of micromolar concentrations of Zn2+. The characteristics of this action suggest that Zn2+ increases the apparent affinity of the receptor for ATP. In addition, Zn2+ increased membrane depolarization and action potential firing elicited by ATP. These observations suggest that Zn2+ may play a physiological role in regulating the excitatory action of ATP on mammalian neurons.