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Wild\u2010type and mutant receptors were expressed in <jats:italic>Xenopus<\/jats:italic> oocytes and analysed with two\u2010electrode voltage clamp. All mutations caused less than a 2\u2010fold change in the EC<jats:sub>50<\/jats:sub> of the ATP concentration\u2010response relation. Decreasing the extracellular pH from 7.5 to 6.5 potentiated the responses to 10 \u03bc<jats:sc>m<\/jats:sc> ATP of wild\u2010type P2X<jats:sub>2<\/jats:sub> and eight mutant receptors more than 4\u2010fold, but the response of the mutant receptor H319A was potentiated only 1.4\u2010fold. The H319A mutation greatly attenuated the maximal potentiation that could be produced by a drop in pH, shifted the p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> (\u2010log of dissociation constant) of the potentiation to a more basic pH as compared with P2X<jats:sub>2<\/jats:sub> and revealed a substantial pH\u2010dependent decrease in the maximum response with a p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> near 6.0. Substituting a lysine for H319 reduced the EC<jats:sub>50<\/jats:sub> for ATP 40\u2010fold. Zinc (20 \u03bc<jats:sc>m<\/jats:sc>) potentiated the responses to 10 \u03bc<jats:sc>m<\/jats:sc> ATP of wild\u2010type P2X<jats:sub>2<\/jats:sub> and seven histidine mutants by \u223c8\u2010fold but had virtually no effect on the responses of two mutants, H120A and H213A. Neither H120A nor H213A removed the voltage\u2010independent inhibition caused by high concentrations of zinc. The observation that different mutations selectively eliminated pH or zinc potentiation implies that there are two independent sites of action, even though the mechanisms of pH and zinc potentiation appear similar.<\/jats:p>","DOI":"10.1113\/jphysiol.2001.013244","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:45:57Z","timestamp":1027773957000},"page":"347-359","source":"Crossref","is-referenced-by-count":81,"title":["The role of histidine residues in modulation of the rat P2X<sub>2<\/sub> purinoceptor by zinc and pH"],"prefix":"10.1113","volume":"539","author":[{"given":"J. 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