Calvert Jennifer A, Evans Richard J
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, LE1 9HN, UK.
Mol Pharmacol. 2004 Jan;65(1):139-48. doi: 10.1124/mol.65.1.139.
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 approximately 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 alpha,beta-methylene ATP (alpha,beta-meATP) sensitive, and in neurons from P2X1 receptor-deficient mice the alpha,beta-meATP response was reduced to 2% of all neurons, demonstrating a direct role for P2X1 subunits. Control alpha,beta-meATP responses were eliminated by high extracellular Ca(2+) 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.
P2X受体在整个神经系统中高度表达，ATP在该系统中已被证明是一种神经递质。本研究的目的是表征颈上神经节交感节后神经元内P2X受体的表达情况。逆转录聚合酶链反应显示所有P2X受体的mRNA均存在，这增加了这些神经节内多个亚基表达的可能性。全细胞膜片钳和钙成像研究显示，约70%的神经元中存在异质性的P2X受体群体。我们认为，特性的异质性可能是由P2X受体的差异表达和/或亚基组成引起的。主要表型为P2X2样；神经元表现出缓慢脱敏、对拮抗剂敏感以及具有P2X2受体特征的离子调节特征：酸化和细胞外Zn2+增强作用，高细胞外Ca2+和pH减弱作用。一小部分神经元（10 - 15%）对α,β-亚甲基ATP（α,β-meATP）敏感，在来自P2X1受体缺陷小鼠的神经元中，α,β-meATP反应降至所有神经元的2%，这表明P2X1亚基具有直接作用。高细胞外Ca(2+)和pH消除了对照α,β-meATP反应，表明存在包含P2X1和P2X2受体特性的异源通道。本研究表明，在神经元中，P2X1受体可影响异源P2X受体的特性。鉴于P2X1受体在一系列神经元中的表达，该亚基对P2X受体特性的调节作用似乎更为广泛。
