ENHANCEMENT OF ATP-ACTIVATED CURRENT BY PROTONS IN DORSAL-ROOT GANGLION NEURONS

The effect of pH on ATP-activated current in bullfrog dorsal root gang lion neurons was studied using the whole-cell patch-clamp technique. A TP-activated current amplitude was highly dependent upon extracellular pH. An acid pH increased, whereas alkaline pH decreased, ATP-activate d current amplitude. The half-maximal pH (EC(50)) for potentiation of 2.5 mu M ATP-activated current was 7.2. Acidification alone did not ac tivate detectable current and, at an acid pH, ATP-activated current wa s abolished by suramin. Proton-induced enhancement of ATP-activated cu rrent was not sensitive to membrane potential between -80 and +40 mV, and did not involve a shift in reversal potential. Lowering pH from 7. 2 to 6.5 or elevating pH from 7.2 to 8.0 shifted the ATP concentration /response curve to the left or right, respectively, without changing t he maximal response to ATP Protons increased the time constant of deac tivation without affecting the time constant of activation or desensit ization of ATP-activated current. Alteration of patch-pipette (intrace llular) pH did not affect the enhancement of ATP-activated current by extracellular protons. Diethylpyrocarbonate (DEP). dithiothreitol (DTT ), 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB), or N-ethylmaleimide (NEM) did not affect enhancement of ATP-activated current by protons. The results suggest that extracellular protons, at physiological conce ntrations, can regulate the function of P-2X purinoceptors by modulati ng the affinity of the ATP-binding site.