Cross-talking between 5-HT3 and GABAA receptors in cultured myenteric neurons

• Published in: Synapse (New York, N.Y.) N.Y.), 2007-09, Vol.61 (9), p.732-740
• Main Authors: Miranda-Morales, Marcela, García-Hernández, Luz M., Ochoa-Cortés, Fernando, Espinosa-Luna, Rosa, Naranjo-Rodríguez, Elia B., Barajas-López, Carlos
• Format: Article
• Language: English
• Subjects: 5-HT3 receptors; Animals; Cells, Cultured; cys-loop receptor superfamily; Drug Interactions; Female; GABA Agents - pharmacology; GABAA receptors; gamma-Aminobutyric Acid - pharmacology; Guinea Pigs; ligand-gated ion channels; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; myenteric neurones; Myenteric Plexus - cytology; Neurons - physiology; neurotransmitters; Patch-Clamp Techniques - methods; protein interactions; Receptors, GABA-A - physiology; Receptors, Serotonin, 5-HT3 - physiology; serotonin (5-HT); Serotonin - pharmacology; Serotonin Agents - pharmacology; γ-aminobutyric acid
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20411

We recorded whole‐cell ion currents induced by γ‐aminobutyric acid (IGABA) and serotonin (I5‐HT) to investigate and characterize putative interactions between GABAA and 5‐HT3 receptors in myenteric neurons from the guinea pig small intestine. IGABA and I5‐HT were inhibited by bicuculline and ondansetron, respectively. Currents induced by the simultaneous application of both, GABA and 5‐HT (IGABA+5‐HT) were significantly lower than the sum of IGABA and I5‐HT, indicating the existence of a current occlusion. Such an occlusion was observed when GABAA and 5‐HT3 receptors are virtually saturated. Kinetics, and pharmacological properties of IGABA+5‐HT indicate that they are mediated by activation of both, GABAA and 5‐HT3 channels. GABA did not alter I5‐HT in neurons without GABAA channels, in the presence of bicuculline (a GABAA receptor antagonist) or at the reversal potential for IGABA. Similarly, 5‐HT did not modify IGABA in neurons in which 5‐HT3 channels were absent, after inhibiting 5‐HT3 channels with ondansetron (a 5‐HT3 receptor antagonist) or at the reversal potential for I5‐HT. Current occlusion was observed as soon as GABAA and 5‐HT3 channels were being activated, in the absence of Ca2+, at low temperature (11°C), and after adding staurosporine (a protein kinase inhibitor) to the pipette solution. Our proposal is that GABAA and 5‐HT3 channels are organized in clusters and within these, both channels can cross‐inhibit each other, likely by allosteric interactions between these proteins. Synapse 61:732–740, 2007. © 2007 Wiley‐Liss, Inc.