DIFFERENT SENSITIVITIES TO PH OF ATP-INDUCED CURRENTS AT 4 CLONED P2XRECEPTORS

The effect of changing extracellular pH was studied on the currents in duced by ATP or alpha beta-methylene-ATP in HEK293 cells transfected w ith different P2X receptor subunits. In cells expressing P2X(1), P2X(3 ), or P2X(4) receptors, the effect of ATP was decreased by acidificati on. In cells expressing P2X(2) receptors, acidification increased the ATP-induced current; this effect was also seen in cells expressing het eromeric P2X(2) and P2X(3) receptors. At P2X(2) receptors, acidificati on caused a leftward shift in the ATP concentration-response curve, wi thout change in maximum; the pK(a) for this effect was 7.3. At P2X(4) receptors, acidification caused a rightward shift in the ATP concentra tion-response curve, without change in the maximum; the pK(a) for this effect was 6.8. The pH dependence of the action of ATP should be take n into account in studies of synaptic transmission, and it may provide a further tool to assign molecular identity to P2X receptors expresse d by brain neurons.