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Cross-talk and Co-trafficking between ρ1/GABA Receptors and ATP-gated Channels *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 279, Issue: 8, Page: 6967-6975
2004
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Article Description

γ-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 ρ1/GABA and the excitatory P2X 2 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 P2X 2 is deleted or in competition experiments with minigenes coding for the C-terminal domain of P2X 2 or the main intracellular loop of ρ1 subunits. We also show a physical interaction between P2X 2 and ρ1 receptors expressed in oocytes and the co-clustering of these receptors in transfected hippocampal neurons. Co-expression with P2X 2 induces retargeting and recruitment of mainly intracellular ρ1/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.

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