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- Title
The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.
- Authors
Stephan, Gabriele; Lumei Huang; Yong Tang; Vilotti, Sandra; Fabbretti, Elsa; Ye Yu; Nörenberg, Wolfgang; Franke, Heike; Gölöncsér, Flóra; Sperlágh, Beáta; Dopychai, Anke; Hausmann, Ralf; Schmalzing, Günther; Rubini, Patrizia; Illes, Peter
- 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.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-03728-5