Stoichiometry of the α9α10 nicotinic cholinergic receptor

Paola V. Plazas, Eleonora Katz, María E. Gomez-Casati, Cecilia Bouzat, Ana Beĺn Elgoyhen

Research output: Contribution to journalArticlepeer-review

Abstract

The α9 and α10 nicotinic cholinergic subunits assemble to form the receptor that mediates synaptic transmission between efferent olivocochlear fibers and hair cells of the cochlea. They are the latest vertebrate nicotinic cholinergic receptor (nAChR) subunits that have been cloned, and their identification has established a distant early divergent branch within the nAChR gene family. The α10 subunit serves as a "structural" component leading to heteromeric α9α10 nAChRs with distinct properties. We now have probed the stoichiometry of recombinant α9α10 nAChRs expressed in Xenopus oocytes. We have made use of the analysis of the population of receptors assembled from a wild-type subunit and its partner α9 or α10 subunit bearing a reporter mutation of a valine to threonine at position 13′ of the second transmembrane domain (TM2). Because the mutation increased the sensitivity of the receptor for acetylcholine (ACh) but mutations at different subunits were not equivalent, the number of α9 and α10 subunits could be inferred from the number of components in compound concentration-response curves to ACh. The results were confirmed via the analysis of the effects of a mutation to threonine at position 17′ of TM2. Because at this position the mutations at different subunits were equivalent, the stoichiometry was inferred directly from the shifts in the ACh EC 50 values. We conclude that the recombinant α9α10 receptor is a pentamer with a (α9)2(α10)3 stoichiometry.

Original languageEnglish (US)
Pages (from-to)10905-10912
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number47
DOIs
StatePublished - Nov 23 2005
Externally publishedYes

Keywords

  • Cholinergic receptors
  • Cochlea
  • Ligand-gated channels
  • Mutagenesis
  • Nicotinic receptors
  • Stoichiometry

ASJC Scopus subject areas

  • Neuroscience(all)

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