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 alphabeta-methylene-ATP in HEK293 cells transfected with different P2X receptor subunits. In cells expressing P2X1, P2X3, or P2X4 receptors, the effect of ATP was decreased by acidification. In cells expressing P2X2 receptors, acidification increased the ATP-induced current; this effect was also seen in cells expressing heteromeric P2X2 and P2X3 receptors. At P2X2 receptors, acidification caused a leftward shift in the ATP concentration-response curve, without change in maximum; the pKa for this effect was 7.3. At P2X4 receptors, acidification caused a rightward shift in the ATP concentration-response curve, without change in the maximum; the pKa 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.
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Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Plan-les-Ouates, 1228 Geneva, Switzerland.
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D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D018408:Patch-Clamp Techniques; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D012680:Sensitivity and Specificity; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate