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Journal of Neuroscience, Vol 16, 448-455, Copyright © 1996 by Society for Neuroscience
A novel neuronal P2x ATP receptor ion channel with widespread distribution in the brain
P Seguela, A Haghighi, JJ Soghomonian and E Cooper
Unite de Neurobiologie, Institut Neurologique de Montreal, Universite McGill, Quebec, Canada.
There is strong evidence that ATP acts as an excitatory neurotransmitter in
the periphery, yet little is known about fast central ATP-mediated
transmission. We report here the molecular cloning of a novel neuronal
ionotropic ATP receptor of the P2x subtype (P2x3) isolated from rat brain.
This central P2x channel subunit has significant amino acid homology with
two recently cloned ATP-gated channels from rat smooth muscle (47%) and
pheochromocytoma PC12 cells (37%). P2x3 receptor contains the
characteristic 10 conserved cysteines of ATP-gated channels, a putative
extracellular region homologous to the Walker type A motif found in various
nucleotide-binding proteins, and two potential sites for phosphorylation by
protein kinase C. Homomeric receptor P2x3 channels expressed in Xenopus
oocytes produce rapid cation-selective purinergic currents that are
potentiated by zinc ions and reversibly blocked by the P2x antagonists
suramin, Reactive Blue 2, and
pyridoxalphosphate-6-axophenyl-2U,4U-disulfonic acid. P2x3- receptor
subunit mRNA is found in the Purkinje cells and the granule cells of the
cerebellum as well as in CA3 pyramidal cells of the hippocampus that are
innervated by zinc-rich axon terminals of mossy fibers. Our results suggest
that fast excitatory synaptic transmission mediated by zinc-sensitive
ATP-gated channels is widespread in mammalian brain.
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