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

Author

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  • Gabriele Stephan

    (University of Leipzig)

  • Lumei Huang

    (University of Leipzig
    Chengdu University of Traditional Chinese Medicine)

  • Yong Tang

    (Chengdu University of Traditional Chinese Medicine)

  • Sandra Vilotti

    (International School for Advanced Studies)

  • Elsa Fabbretti

    (University of Trieste)

  • Ye Yu

    (Institute of Neuroscience and State Key Laboratory of Neuroscience)

  • Wolfgang Nörenberg

    (University of Leipzig)

  • Heike Franke

    (University of Leipzig)

  • Flóra Gölöncsér

    (Hungarian Academy of Sciences
    Semmelweis University School of PhD Studies)

  • Beáta Sperlágh

    (Hungarian Academy of Sciences)

  • Anke Dopychai

    (Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University)

  • Ralf Hausmann

    (Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University)

  • Günther Schmalzing

    (Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University)

  • Patrizia Rubini

    (University of Leipzig)

  • Peter Illes

    (University of Leipzig)

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.

Suggested Citation

  • Gabriele Stephan & Lumei Huang & Yong Tang & Sandra Vilotti & Elsa Fabbretti & Ye Yu & Wolfgang Nörenberg & Heike Franke & Flóra Gölöncsér & Beáta Sperlágh & Anke Dopychai & Ralf Hausmann & Günther Sc, 2018. "The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03728-5
    DOI: 10.1038/s41467-018-03728-5
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