The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel

Gabriele Stephan, Lumei Huang, Yong Tang, Sandra Vilotti, Elsa Fabbretti, Ye Yu, Wolfgang Nörenberg, Heike Franke, Flóra Göröncsér, Beáta Sperlágh, Anke Dopychai, Ralf Hausmann, Günther Schmalzing, Patrizia Rubini, Peter Illes

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Two subclasses of acid-sensing ion channels (ASIC3) and of ATP-sensitive P2X receptors (P2X3Rs) show a partially overlapping expression in sensory neurons. Here we report that both recombinant and native receptors interact with each other in multiple ways. Current measurements with the patch-clamp technique prove that ASIC3 stimulation strongly inhibits the P2X3R current partly by a Ca2+-dependent mechanism. The proton-binding site is critical for this effect and the two receptor channels appear to switch their ionic permeabilities during activation. Co-immunoprecipation proves the close association of the two protein structures. BN-PAGE and SDS-PAGE analysis is also best reconciled with the view that ASIC3 and P2X3Rs form a multiprotein structure. Finally, in vivo measurements in rats reveal the summation of pH and purinergically induced pain. In conclusion, the receptor subunits do not appear to form a heteromeric channel, but tightly associate with each other to form a protein complex, mediating unidirectional inhibition.

Original languageEnglish
Article number1354
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Stephan, G., Huang, L., Tang, Y., Vilotti, S., Fabbretti, E., Yu, Y., Nörenberg, W., Franke, H., Göröncsér, F., Sperlágh, B., Dopychai, A., Hausmann, R., Schmalzing, G., Rubini, P., & Illes, P. (2018). The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel. Nature communications, 9(1), [1354]. https://doi.org/10.1038/s41467-018-03728-5