intracellular motif of P2X₃ receptors is required for functional cross-talk with GABAA receptors in nociceptive DRG neurons

• Published in: Journal of neurochemistry Vol. 102; no. 4; pp. 1357 - 1368
• Main Authors: Toulmé, Estelle, Blais, Dominique, Léger, Claire, Landry, Marc, Garret, Maurice, Séguéla, Philippe, Boué-Grabot, Eric
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.08.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: ATP; Biochemistry; Biological and medical sciences; Cell culture; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Fundamental and applied biological sciences. Psychology; GABA receptor; Ions; Molecular and cellular biology; Molecular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Neurosciences; Neurotransmitters; pain; purinoceptor; Rodents; sensory neurons; transmitter-gated channels; Vertebrates: nervous system and sense organs; Ionotropic receptor; pain; P2X3 purinergic receptor; Rat; Rodentia; Central nervous system; GABA receptor; purinoceptor; sensory neurons; Vertebrata; Mammalia; Modulation; Information processing; Sensory neuron; P2X purinergic receptor; Coupling; Intracellular; ATP; Gabaergic receptor A; Subtype; transmitter-gated channels; Biological receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04640.x

Functional cross-talk between structurally unrelated P2X ATP receptors and members of the 'cys-loop' receptor-channel superfamily represents a recently-discovered mechanism for rapid modulation of information processing. The extent and the mechanism of the inhibitory cross-talks between these two classes of ionotropic receptors remain poorly understood, however. Both ionic and molecular coupling were proposed to explain cross-inhibition between P2X subtypes and GABAA receptors, suggesting a P2X subunit-dependent mechanism. We show here that cross-inhibition between neuronal P2X₃ or P2X₂₊₃ and GABAA receptors does not depend on chloride and calcium ions. We identified an intracellular QST³⁸⁶⁻³⁸⁸ motif in P2X₃ subunits which is required for the functional coupling with GABAA receptors. Moreover the cross-inhibition between native P2X₃ and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is abolished by infusion of a peptide containing the QST motif as well as by viral expression of the main intracellular loop of GABAAβ3 subunits. We provide evidence that P2X₃ and GABAA receptors are colocalized in the soma and central processes of nociceptive DRG neurons, suggesting that specific intracellular P2X₃-GABAA subunit interactions underlie a pre-synaptic cross-talk that might contribute to the regulation of sensory synaptic transmission in the spinal cord.