Abstract

P2X receptors are highly expressed throughout the nervous system, where ATP has been shown to be a neurotransmitter. The aim of this study was to characterize P2X receptor expression within sympathetic postganglionic neurons from the superior cervical ganglia. Reverse transcription-polymerase chain reaction showed the presence of mRNA for all P2X receptors, raising the possibility of multiple subunit expression within these ganglia. Whole-cell patch-clamp and calcium imaging studies revealed a heterogeneous population of P2X receptors in ∼70% of neurons. We propose that the heterogeneity in properties could be caused by differential expression and/or subunit composition of the P2X receptor. The dominant phenotype was P2X₂-like; neurons showed slow desensitization, sensitivity to antagonists, and a profile of ionic modulation that is characteristic of P2X₂ receptors: potentiation by acidification and extracellular Zn²⁺ and attenuation by high extracellular Ca²⁺ and pH. A subpopulation of neurons (10-15%) were α,β-methylene ATP (α,β-meATP) sensitive, and in neurons from P2X₁ receptor-deficient mice the α,β-meATP response was reduced to 2% of all neurons, demonstrating a direct role for P2X₁ subunits. Control α,β-meATP responses were eliminated by high extracellular Ca²⁺ and pH, indicating the presence of heteromeric channels incorporating the properties of P2X₁ and P2X₂ receptors. This study demonstrates that in neurons, the P2X₁ receptor can contribute to the properties of heteromeric P2X receptors. Given the expression of P2X₁ receptors in a range of neurons, it seems likely that regulation of the properties of P2X receptors by this subunit is more widespread.