Non-synaptic release of ATP by electrical stimulation in slices of rat hippocampus, cerebellum and habenula

ATP is thought to be a fast neurotransmitter in the medial habenula region of the brain, and may be coreleased with other transmitters, for example with glutamate in the hippocampus. We monitored ATP release in rat brain slices using the bioluminescent indicator system luciferin-luciferase. Electrical stimulation of the hippocampus, cerebellum or habenula led to ATP release, but this release was calcium-independent and was not blocked by tetrodotoxin, or by other agents found to block ATP release from red blood cells. Although calcium-dependent ATP release may occur in response to electrical stimulation, it appears to be overwhelmed by calcium-independent release, which may result from electroporation of cells close to the stimulating electrode. Consistent with this, uptake into cells of the fluorescent dye Lucifer yellow was promoted by electrical stimulation. Our data undermine a previous suggestion, based on use of the luciferin-luciferase technique, that ATP is synaptically released with glutamate in the hippocampus.