Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors

The effect of changing extracellular pH was studied on the currents induced by ATP or alpha beta-methylene-ATP in HEK293 cells transfected with different P2X receptor subunits. In cells expressing P2X(1), P2X(3), or P2X(4) receptors, the effect of ATP was decreased by acidification. In cells expressing P2X(2) receptors, acidification increased the ATP-induced current; this effect was also seen in cells expressing heteromeric P2X(2) and P2X(3) receptors. At P2X(2) receptors, acidification caused a leftward shift in the ATP concentration-response curve, without change in maximum; the pK(a) for this effect was 7.3. At P2X(4) receptors, acidification caused a rightward shift in the ATP concentration-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 taken into account in studies of synaptic transmission, and it may provide a further tool to assign molecular identity to P2X receptors expressed by brain neurons.