Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels.
J. Biol. Chem.. 2004-09-29; 279(50): 52517-52525
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1. J Biol Chem. 2004 Dec 10;279(50):52517-25. Epub 2004 Sep 29.
Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2
Boué-Grabot E(1), Toulmé E, Emerit MB, Garret M.
(1)Laboratoire de Neurophysiologie, CNRS Unité Miate de Recherche UMR 5543,
Université Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France.
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
PMID: 15456793 [Indexed for MEDLINE]