Heterogeneity of P2X Receptors in Sympathetic Neurons: Contribution of Neuronal P2X1 Receptors Revealed Using Knockout Mice

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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.