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Zn2+ potentiates excitatory action of ATP on mammalian neurons
C Li1, R W Peoples, Z Li
1Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852.
Abstract:
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.