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Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels.
Boué-Grabot, Eric; Toulmé, Estelle; Emerit, Michel B; Garret, Maurice.
Afiliación
  • Boué-Grabot E; Laboratoire de Neurophysiologie, CNRS Unité Miate de Recherche UMR 5543, Université Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France. eric.boue-grabot@umr5543.u-bordeaux2.fr
J Biol Chem ; 279(50): 52517-25, 2004 Dec 10.
Article en En | MEDLINE | ID: mdl-15456793
ATP and gamma-aminobutyric acid (GABA) are two fast neurotransmitters co-released at central synapses, where they co-activate excitatory P2X and inhibitory GABAA (GABA type A) receptors. We report here that co-activation of P2X2 and various GABAA receptors, co-expressed in Xenopus oocytes, leads to a functional cross-inhibition dependent on GABAA subunit composition. Sequential applications of GABA and ATP revealed that alphabeta- or alphabetagamma-containing GABAA receptors inhibited P2X2 channels, whereas P2X2 channels failed to inhibit gamma-containing GABAA receptors. This functional cross-talk is independent of membrane potential, changes in current direction, and calcium. Non-additive responses observed between cation-selective GABAA and P2X2 receptors further indicate the chloride independence of this process. Overexpression of minigenes encoding either the C-terminal fragment of P2X2 or the intracellular loop of the beta3 subunit disrupted the functional cross-inhibition. We previously demonstrated functional and physical cross-talk between rho1 and P2X2 receptors, which induced a retargeting of rho1 channels to surface clusters when co-expressed in hippocampal neurons (Boue-Grabot, E., Emerit, M. B., Toulme, E., Seguela, P., and Garret, M. (2004) J. Biol. Chem. 279, 6967-6975). Co-expression of P2X2 and chimeric rho1 receptors with the C-terminal sequences of alpha2, beta3, or gamma2 subunits indicated that only rho1-beta3 and P2X2 channels exhibit both functional cross-inhibition in Xenopus oocytes and co-clustering/retargeting in hippocampal neurons. Therefore, the C-terminal domain of P2X2 and the intracellular loop of beta GABAA subunits are required for the functional interaction between ATP- and GABA-gated channels. This gamma subunit-dependent cross-talk may contribute to the regulation of synaptic activity.
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Purinérgicos P2 / Receptores de GABA-A Límite: Animals / Female / Humans Idioma: En Revista: J Biol Chem Año: 2004 Tipo del documento: Article País de afiliación: Francia
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Purinérgicos P2 / Receptores de GABA-A Límite: Animals / Female / Humans Idioma: En Revista: J Biol Chem Año: 2004 Tipo del documento: Article País de afiliación: Francia