Loading...
Please wait, while we are loading the content...
Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sherwood, Thomas W. Lee, Kirsten G. Gormley, Matthew G. Askwith, Candice C. |
| Copyright Year | 2011 |
| Abstract | Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the CNS, and activation of ASIC1a homomeric channels induces neuronal death after local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that coexpression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the nonselective potassium channel blockers tetraethylammonium and barium. In addition, steady-state desensitization is induced at more basic pH values, and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution, and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Furthermore, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury after stroke. |
| File Format | PDF HTM / HTML |
| DOI | 10.1523/JNEUROSCI.1665-11.2011 |
| PubMed reference number | 21715637 |
| Journal | Medline |
| Volume Number | 31 |
| Issue Number | 26 |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/31/26/9723.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1523/JNEUROSCI.1665-11.2011 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
