ELECTROPHYSIOLOGICAL PROPERTIES OF P-2X-PURINOCEPTORS IN RAT SUPERIOR CERVICAL, NODOSE AND GUINEA-PIG CELIAC NEURONS

1. Whole-cell recordings were made from guinea-pig coeliac, rat nodose and rat superior cervical (SCG) neurones in culture, and currents in response to fast-flow (concentration clamp) application of ATP and other ATP analogues were measured. 2. At a holding potential of -70 mV, ATP evoked inward currents in all neurones. ATP-induced currents reversed at approximately 0 mV and showed strong inward rectification. Halving the external sodium concentration shifted the reversal potential by -15 to -17 mV, while increasing external potassium from 2 to 20 mar produced a 6-10 mV shift in reversal potential. Latency to onset of ATP current was < 1 ms; rise time was concentration dependent with maximum time to peak of 5-20 ms in nodose and coeliac neurones but 80 ms in superior cervical neurones. 3. Threshold concentrations of ATP were 0.1 mu M for nodose and coeliac neurones but 10 mu M for superior cervical neurones; EC(50) values were approximately 3 mu M for both nodose and coeliac neurones and 43 mu M for superior cervical ganglia. Hill slopes for ATP concentration-response curves were not significantly different from unity in nodose and coeliac neurones whereas the Hill slope in superior cervical neurones was two. 4. 2-MethylthioATP (2-MeSATP) acted as a full agonist in all three neuronal preparations; EC(50) values were 0.4, 2.8 and 46 mu M for nodose, coeliac and superior cervical neurones, respectively. alpha,beta-Methylene ATP (alpha,beta-MeATP) was a full agonist in nodose and coeliac neurones with EC(50) values of 9 and 13 mu M, respectively. 5. In superior cervical neurones alpha,beta-MeATP had little or no agonist action but produced a concentration-dependent attenuation of the ATP current. Thus, alpha,beta-MeATP appears to behave as a partial agonist at P-ax-purinoceptors in superior cervical neurones. 6. The non-selective purinoceptor antagonists suramin (1-100 mu M) and pyridoxal-5'-phosphate (30 mu M), as well as the putative P-2Y-selective antagonist, Cibacron Blue (30 mu M), inhibited all agonist-evoked responses to a similar degree in all three neuronal populations. 7. This study demonstrates that an agonist potency profile of 2-MeSATP greater than or equal to ATP greater than or equal to alpha,beta-MeATP is characteristic of ligand-gated P-2X-purinoceptors in isolated peripheral neurones. We also suggest that the P-2X-receptor in superior cervical neurones may represent a distinct subtype of P-2X-purinoceptor from that present in nodose and coeliac neurones.