Intracellular cross talk and physical interaction between two classes of neurotransmitter-gated channels.
Fast chemical communications in the nervous system are mediated by several classes of receptor channels believed to be independent functionally and physically. We show here that concurrent activation of P2X2 ATP-gated channels and 5-HT3 serotonin-gated channels leads to functional interaction and nonadditive currents (47-73% of the predicted sum) in mammalian myenteric neurons as well as in Xenopus oocytes or transfected human embryonic kidney (HEK) 293 cell heterologous systems. We also show that these two cation channels coimmunoprecipitate constitutively and are associated in clusters. In heterologous systems, the inhibitory cross talk between P2X2 and 5-HT3 receptors is disrupted when the intracellular C-terminal domain of the P2X2 receptor subunit is deleted and when minigenes coding for P2X2 or 5-HT3A receptor subunit cytoplasmic domains are overexpressed. Injection of fusion proteins containing the C-terminal domain of P2X2 receptors in myenteric neurons also disrupts the functional interaction between native P2X2 and 5-HT3 receptors. Therefore, activity-dependent intracellular coupling of distinct receptor channels underlies ionotropic cross talks that may significantly contribute to the regulation of neuronal excitability and synaptic plasticity.
Boué-Grabot
Eric
E
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4.
Barajas-López
Carlos
C
Chakfe
Yassar
Y
Blais
Dominique
D
Bélanger
Danny
D
Emerit
Michel B
MB
Séguéla
Philippe
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D004553:Electric Conductivity; D006168:Guinea Pigs; D006801:Humans; D015640:Ion Channel Gating; D009197:Myenteric Plexus / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D020239:Receptor Cross-Talk; D011978:Receptors, Nicotinic / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D058476:Receptors, Purinergic P2X2; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014981:Xenopus
C546401:P2RX2 protein, human; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; D000255:Adenosine Triphosphate