Allosteric modulation of native cochlear P2X receptors: Insights from comparison with recombinant P2X2 receptors

Kanjhan, Refik, Raybould N. P., Jagger D. J., Greenwood D. and Housley G. D. (2003) Allosteric modulation of native cochlear P2X receptors: Insights from comparison with recombinant P2X2 receptors. Audiology and Neuro-Otology, 8 3: 115-128. doi:10.1159/000069478

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Author Kanjhan, Refik
Raybould N. P.
Jagger D. J.
Greenwood D.
Housley G. D.
Title Allosteric modulation of native cochlear P2X receptors: Insights from comparison with recombinant P2X2 receptors
Formatted title
Allosteric modulation of native cochlear P2X receptors: Insights from comparison with recombinant P2X2 receptors
Journal name Audiology and Neuro-Otology   Check publisher's open access policy
ISSN 1420-3030
Publication date 2003
Year available 2003
Sub-type Article (original research)
DOI 10.1159/000069478
Volume 8
Issue 3
Start page 115
End page 128
Total pages 14
Publisher Karger Medical and Scientific Publishers
Language eng
Subject 1109 Neurosciences
Abstract Extracellular adenosine 5'-triphosphate (ATP)-gated ion channels assembled from P2X receptor subunits exhibit subunit-selective allosteric modulation by protons and divalent cations. In voltage-clamped guinea-pig cochlear outer hair cells (OHC) and Deiters' cells (DC), H+ and Cu2+, but not Zn2+, enhanced the P2X receptor-mediated inward currents. Acid pH (6.5) potentiated OHC ATP-gated currents by 45%. Co-application of Cu2+ (1-40 muM) with ATIP increased the response by 20%. In DCs, ATP-gated currents were potentiated 85% by acid pH, and 70% by Cu2+. Alkaline pH inhibited ATP-gated inward currents by 73% in CHCs and 85% in DCs. Zn2+ was either ineffective (1-10 muM) or inhibitory (40-400 muM). Recombinant rat P2X(2) receptor-mediated inward currents in Xenopus oocytes displayed allosteric modulation that was different from the native guinea-pig cochlear P2X receptors. The oocyte ATP-gated inward current was potentiated 450% by shifting from pH 7.5 to pH 6.5, and 130% with 40 muM Cu2+. The enhanced response to ATP with acid pH and Cu2+ is a signature of the P2X(2) subunit. In contrast to native guinea-pig cochlear cells, extracellular Zn2+ (40 muM) increased the recombinant ATP-gated inward current by 200% in oocytes. These results suggest that the positive allosteric modulation of cochlear OHC and DC ATP-gated ion channels by protons and Cu2+ arises in part from the P2X(2) receptor subunit, with additional regulatory elements.
Formatted abstract
Extracellular adenosine 5'-triphosphate (ATP)-gated ion channels assembled from P2X receptor subunits exhibit subunit-selective allosteric modulation by protons and divalent cations. In voltage-clamped guinea-pig cochlear outer hair cells (OHC) and Deiters' cells (DC), H+ and Cu2+, but not Zn2+, enhanced the P2X receptor-mediated inward currents. Acid pH (6.5) potentiated OHC ATP-gated currents by 45%. Co-application of Cu2+ (1-40 µM) with ATP increased the response by 20%. In DCs, ATP-gated currents were potentiated 85% by acid pH, and 70% by Cu2+. Alkaline pH inhibited ATP-gated inward currents by 73% in OHCs and 85% in DCs. Zn2+ was either ineffective (1-10 µM) or inhibitory (40-400 µM). Recombinant rat P2X2 receptor-mediated inward currents in Xenopus oocytes displayed allosteric modulation that was different from the native guinea-pig cochlear P2X receptors. The oocyte ATP-gated inward current was potentiated 450% by shifting from pH 7.5 to pH 6.5, and 130% with 40 µM Cu2+. The enhanced response to ATP with acid pH and Cu2+ is a signature of the P2X2 subunit. In contrast to native guinea-pig cochlear cells, extracellular Zn2+ (40 µM) increased the recombinant ATP-gated inward current by 200% in oocytes. These results suggest that the positive allosteric modulation of cochlear OHC and DC ATP-gated ion channels by protons and Cu2+ arises in part from the P2X2 receptor subunit, with additional regulatory elements.
Keyword Hearing
Hair Cells
Extracellular adenosine-triphosphate
Adenosine-triphosphate-gated ion channel
Zinc
Copper
pH
Allosteric modulation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Journal name change in 2005 to Audiology and Neurotology: basic research and clinical applications

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 10 Apr 2006, 23:47:48 EST