Full sensitivity of P2X2 purinoceptor to ATP revealed by changing extracellular pH

Abstract

A full pharmacological characterization was carried out on a recombinant ATP-gated ion channel (P2X2 purinoceptor) expressed in Xenopus oocytes. This slowly-desensitizing neuronal P2X2 purinoceptor, activated by ATP (EC50 = 4.6 ± 1 μM at pH 7.4; n = 4), showed the agonist potency order: ATP ≥ 2-MeSATP = ATPγS≥ATPαS>>Bz-ATP. The receptor affinity for ATP was enhanced 5-10 fold by acidifying the bathing solution (to pH 6.5) but was diminished 4-5 fold in an alkaline solution (pH 8.0). The maximum activity of P2X2 purinoceptors and the activity order of a series of nucleotides were unaltered by changing extracellular pH. Interestingly, ATP sensitivity at a recombinant P2Y1 purinoceptor remained unaltered with changing extracellular pH. These results indicate that acidotic conditions in the synaptic cleft could strengthen purinergic transmission at neuronal P2X2 purinoceptors.