The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29636447.
- Also identified by DOI 10.1038/s41467-018-03728-5 and PMC identifier 5893604.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 Ca<sup>2+</sup>-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.
Medical subject headings
- Acid Sensing Ion Channels
- Calcium
- Ganglia, Spinal
- Hyperalgesia
- Pain
- Protons
- Receptors, Purinergic P2X3