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

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2018-04, Vol.9 (1), p.1354-18, Article 1354
Main Authors: Stephan, Gabriele, Huang, Lumei, Tang, Yong, Vilotti, Sandra, Fabbretti, Elsa, Yu, Ye, Nörenberg, Wolfgang, Franke, Heike, Gölöncsér, Flóra, Sperlágh, Beáta, Dopychai, Anke, Hausmann, Ralf, Schmalzing, Günther, Rubini, Patrizia, Illes, Peter
Format: Article
Language:English
Subjects:
13/1
13/106
13/51
14/19
38/109
38/70
631/378/2586
631/378/340
631/378/87
9/74
Acidity
Binding sites
Calcium
Calcium ions
Gel electrophoresis
Humanities and Social Sciences
Ion channels
multidisciplinary
Pain
Purine P2X receptors
Receptor channels
Receptors
Rodents
Science
Science (multidisciplinary)
Sensory neurons
Sodium channels
Sodium lauryl sulfate
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Ca 2+ -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. Two subclasses of ligand-gated ion channels (ASIC3 and P2X3) are both present at sensory neurons and might be therefore subject to receptor crosstalk. Here authors use electrophysiology, biochemistry and co-immunoprecipitation to show that the two ion channels interact and affect P2X3 currents.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-03728-5