Zn2+ potentiates excitatory action of ATP on mammalian neurons.

• DOI: 10.1073/pnas.90.17.8264
• Publication Date: 2006-05-31T12:29:36Z
• Authors: C Li; R W Peoples; Z Li; F F Weight
• Keywords: Male; Neurons; 0301 basic medicine; Ganglia, Sympathetic; Dose-Response Relationship, Drug; Drug Synergism; In Vitro Techniques; Ion Channels; Membrane Potentials; Rats; Rats, Sprague-Dawley; Zinc; 03 medical and health sciences; Adenosine Triphosphate; Animals

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.