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The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-18 (2018), Nature Communications 9, 1354 (2018). doi:10.1038/s41467-018-03728-5, Nature Communications
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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.
- Subjects :
- Male
0301 basic medicine
Patch-Clamp Techniques
Sensory Receptor Cells
Science
Pain
General Physics and Astronomy
Stimulation
CHO Cells
Molecular neuroscience
General Biochemistry, Genetics and Molecular Biology
Xenopus laevis
03 medical and health sciences
Cricetulus
0302 clinical medicine
Protein structure
Cellular neuroscience
Ganglia, Spinal
Animals
Patch clamp
Rats, Wistar
Author Correction
Receptor
lcsh:Science
Ion channel
Multidisciplinary
Chemistry
General Chemistry
Hydrogen-Ion Concentration
Rats
3. Good health
Acid Sensing Ion Channels
body regions
Protein Subunits
030104 developmental biology
Animals, Newborn
Hyperalgesia
Oocytes
Biophysics
Ligand-gated ion channel
Calcium
lcsh:Q
Protons
Ion Channel Gating
Receptors, Purinergic P2X3
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....856e1a54259ec99a7206dfc20e5e51ef
- Full Text :
- https://doi.org/10.1038/s41467-018-03728-5