Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels

J Biol Chem. 2004 Feb 20;279(8):6967-75. doi: 10.1074/jbc.M307772200. Epub 2003 Dec 1.


Gamma-aminobutyric-acid (GABA) and ATP ionotropic receptors represent two structurally and functionally different classes of neurotransmitter-gated channels involved in fast synaptic transmission. We demonstrate here that, when the inhibitory rho1/GABA and the excitatory P2X2 receptor channels are co-expressed in Xenopus oocytes, activation of one channel reduces the currents mediated by the other one. This reciprocal inhibitory cross-talk is a receptor-mediated phenomenon independent of agonist cross-modulation, membrane potential, direction of ionic flux, or channel densities. Functional interaction is disrupted when the cytoplasmic C-terminal domain of P2X2 is deleted or in competition experiments with minigenes coding for the C-terminal domain of P2X2 or the main intracellular loop of rho1 subunits. We also show a physical interaction between P2X2 and rho1 receptors expressed in oocytes and the co-clustering of these receptors in transfected hippocampal neurons. Co-expression with P2X2 induces retargeting and recruitment of mainly intracellular rho1/GABA receptors to surface clusters. Therefore, molecular and functional cross-talk between inhibitory and excitatory ligand-gated channels may regulate synaptic strength both by activity-dependent current occlusion and synaptic receptors co-trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Electrophysiology
  • Immunohistochemistry
  • Ions
  • Ligands
  • Membrane Potentials
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neurons / metabolism
  • Oocytes / metabolism
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Receptors, GABA-B / chemistry*
  • Receptors, GABA-B / metabolism
  • Receptors, Purinergic P2 / chemistry
  • Receptors, Purinergic P2X2
  • Transfection
  • Xenopus / metabolism
  • gamma-Aminobutyric Acid / pharmacology
  • rho GTP-Binding Proteins / chemistry*
  • rho GTP-Binding Proteins / metabolism


  • Ions
  • Ligands
  • Receptors, GABA-B
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X2
  • gamma-Aminobutyric Acid
  • Adenosine Triphosphate
  • rho GTP-Binding Proteins
  • Calcium