A novel neuronal P2x ATP receptor ion channel with widespread distribution in the brain

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 centra...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 1996-01, Vol.16 (2), p.448-455
Main Authors: Seguela, P, Haghighi, A, Soghomonian, JJ, Cooper, E
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Amino Acid Sequence
Animals
Base Sequence
Brain Chemistry - genetics
Cloning, Molecular
In Situ Hybridization
Ion Channels - genetics
Ion Channels - physiology
Molecular Sequence Data
Oocytes - physiology
Patch-Clamp Techniques
Polymerase Chain Reaction
Rats
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - physiology
Xenopus
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.16-02-00448.1996