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The Journal of Neuroscience, September 15, 1998, 18(18):7152-7159
Central P2X4 and P2X6 Channel Subunits
Coassemble into a Novel Heteromeric ATP Receptor
Khanh-Tuoc
Lê,
Kazimierz
Babinski, and
Philippe
Séguéla
Cell Biology of Excitable Tissue Group, Montreal Neurological
Institute, McGill University, Montreal, Quebec, Canada H3A
2B4
Ionotropic ATP receptors are widely expressed in mammalian
CNS. Despite extensive functional characterization of neuronal homomeric P2X receptors in heterologous expression systems, the subunit
composition of native central P2X ATP-gated channels remains to be
elucidated. P2X4 and P2X6 are major central
subunits with highly overlapping mRNA distribution at both regional and
cellular levels. When expressed alone in Xenopus
oocytes, P2X6 subunits do not assemble into surface
receptors responsive to ATP applications. On the other hand,
P2X4 subunits assemble into bona fide ATP-gated channels,
slowly desensitizing and weakly sensitive to the partial agonist
 , -methylene ATP and to noncompetitive antagonists suramin and
pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid. We demonstrate
here that the coexpression of P2X4 and P2X6
subunits in Xenopus oocytes leads to the generation of a
novel pharmacological phenotype of ionotropic ATP receptors.
Heteromeric P2X4+6 receptors are activated by
low-micromolar ,-methylene ATP (EC50 = 12 µM) and are blocked by suramin and by Reactive Blue 2, which has the property, at low concentrations, to potentiate homomeric P2X4 receptors. The assembly of P2X4 with
P2X6 subunits results from subunit-dependent interactions,
as shown by their specific copurification from HEK-293 cells
transiently transfected with various epitope-tagged P2X channel
subunits. Our data strongly suggest that the numerous cases of neuronal
colocalizations of P2X4 and P2X6 subunits
observed in mammalian CNS reflect the native expression of heteromeric
P2X4+6 channels with unique functional properties.
Key words:
purinoceptor; nucleotide; transmitter-gated cation
channel; , methylene ATP; suramin; PPADS
Copyright © 1998 Society for Neuroscience 0270-6474/98/18187152-08$05.00/0
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