Functional interactions between nicotinic and P2X receptors in celiac ganglia neurons

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.