The α9α10 nicotinic acetylcholine receptor is permeable to and is modulated by divalent cations

Noelia Weisstaub, Douglas E. Vetter, Ana Belén Elgoyhen, Eleonora Katz

Research output: Contribution to journalArticlepeer-review

Abstract

The native cholinergic receptor that mediates synaptic transmission between olivocochlear fibers and outer hair cells of the cochlea is permeable to Ca2+ and is thought to be composed of both the α9 and the α10 cholinergic nicotinic subunits. The aim of the present work was to study the permeability of the recombinant α9α10 nicotinic acetylcholine receptor to Ca2+, Ba2+ and Mg2+ and its modulation by these divalent cations. Experiments were performed, by the two-electrode voltage-clamp technique, in Xenopus laevis oocytes injected with α9 and α10 cRNA. The relative divalent to monovalent cation permeability was high (∼10) for Ca2+, Ba2+ and Mg2+. Currents evoked by acetylcholine (ACh) were potentiated by either Ca2+ or Ba2+ up to 500 μM but were blocked by higher concentrations of these cations. Potentiation by Ca2+ was voltage-independent, whereas blockage was stronger at hyperpolarized than at depolarized potentials. Mg2+ did not potentiate but it blocked ACh-evoked currents (IC50=0.38 mM). In the absence of Ca2+, the EC50 for ACh was higher (48 μM) than that obtained with 1.8 mM Ca2+ (14.3 μM), suggesting that potentiation by Ca2+ involves changes in the apparent affinity of the α9α10 receptor for ACh.

Original languageEnglish (US)
Pages (from-to)122-135
Number of pages14
JournalHearing Research
Volume167
Issue number1-2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Ca permeability
  • Ligand-gated channel
  • Neurotransmitter receptor channel
  • Nicotinic receptor
  • Olivocochlear efferent synapse
  • Outer hair cell
  • Voltage-dependent blockage

ASJC Scopus subject areas

  • Sensory Systems

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