PROTON POTENTIATION OF ATP-GATED ION-CHANNEL RESPONSES TO ATP AND ZN2+ IN RAT NODOSE GANGLION NEURONS

1. The modulation by protons of ATP-gated ion channel responses to ATP and Zn2+ was studied in freshly isolated rat nodose ganglion neurons using the whole cell parch-clamp technique. 2. Reduced external pH enh anced, whereas elevated external pH suppressed, current activated by 1 0 mu M ATP. The pH producing the half-maximal effect (EC(50)) at this ATP concentration was 7.1. 3. Acidification shifted the ATP concentrat ion-response curve to the left, decreasing the EC(50) for ATP, and alk alinization shifted the ATP concentration-response curve to the right, increasing the EC(50) for ATP. Fitting the data to a single-site pH m odel yielded an apparent pk(a) of the site on the ATP-gated ion channe l of 7.6. Between PH 6.8 and 7.8, a change of 0.1 DH unit was calculat ed to change the ATP EC(50) by 4.03 mu M. Changing pH did not alter th e maximal response to ATP. 4. The potentiating effect of protons appea red to be due to a direct action on the ATP-gated channel, as it could not be explained by an increase in the concentration of one or more s pecies of ATP. 5. Lowering PH also increased the potency of Zn2+ for e nhancement of ATP-activated current without altering its maximal respo nse. Changing the pH from 7.3 to 6.8 changed the Zn2+ EC(50) from 12 t o 1.7 mu M. 6. The potentiation of ATP-activated current by protons co uld not be attributed solely to an increase in the affinity of the rec eptor for Zn2+, as the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethy l)ethylenediamine did not alter the effect of protons. 7. Protons and Zn2+ do not appear to act at the same site on ATP-gated channels. as r esponses to maximally effective concentrations of Zn2+ were enhanced f urther by protons and vice verse. 8. These results suggest that proton s regulate the function of P2X purinoceptors in rat nodose ganglion ne urons by modulating the affinity of the binding sites for ATP and Zn2 on these receptor channels.