Functional interactions between nicotinic and P2X receptors in celiac ganglia neurons

• Published in: Autonomic neuroscience 2010-04, Vol.154 (1), p.59-65
• Main Authors: OCHOA-CORTES, Fernando, GARCIA-HERNANDEZ, Luz Maria, ESPINOSA-LUNA, Rosa, MIRANDA-MORALES, Marcela, MONTANO, Luis M, BARAJAS-LOPEZ, Carlos
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholine - pharmacology; Adenosine Triphosphate - pharmacology; Advanced Basic Science; Animals; ATP; Biological and medical sciences; Biophysics; Calcium - metabolism; Cholinergic Agents - pharmacology; Drug Interactions; Electric Stimulation - methods; Electrophysiology; Fundamental and applied biological sciences. Psychology; Ganglia, Sympathetic - cytology; Guinea Pigs; In Vitro Techniques; Ion channels; Ionotropic receptors; Kinetics; Ligand-gated ion channel; Medical Education; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques - methods; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Phosphorylation - drug effects; Phosphorylation - physiology; Protein interactions; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate - analogs & derivatives; Pyridoxal Phosphate - pharmacology; Receptors, Nicotinic - physiology; Receptors, Purinergic P2 - physiology; Receptors, Purinergic P2X; Sympathetic neurons; Vertebrates: nervous system and sense organs
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2009.11.007

Abstract Here we characterized the cross-inhibitory interactions between nicotinic and P2X receptors of celiac neurons from the guinea pig by recording whole-cell currents induced by 1 mM ACh ( IACh ), 1 mM ATP ( IATP ) and by the simultaneous application of both agonists ( IACh + ATP ). IACh and IATP were inhibited by hexamethonium (nicotinic channel blocker) and PPADS (P2X receptor antagonist), respectively. The amplitude of IACh + ATP was equal to the current induced by the most effective agonist, indicating a current occlusion. Various observations indicate that IACh + ATP is carried out through both nicotinic (nACh) and P2X channels: i) IACh + ATP desensitisation kinetics were in between that of IACh and IATP ; ii) application of ATP + ACh, decreased IACh and IATP , whereas no cross-desensitisation was observed between nACh and P2X receptors; iii) ATP did not affect IACh in the presence of PPADS or after P2X receptor desensitisation; and iv) ACh did not affect IATP when nACh channels were blocked with hexamethonium or after nACh receptor desensitisation. Current occlusion is not mediated by activation of metabotropic receptors as it is: i) voltage dependent (was not observed at + 5 mV); ii) present at low temperature (10 °C) and after inhibition of protein kinase activity (with staurosporine); and iii) absent at 30 µM ATP and 30 µM ACh (concentrations that should activate metabotropic receptors). In conclusion, current occlusion described here is similar to the previously reported myenteric neurons. This occlusion is likely the result of allosteric interactions between these receptors.