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

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 alpha9 and the alpha10 cholinergic nicotinic subunits. The aim of the present work was to study the permeability of the recombinant alpha9alpha10 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 alpha9 and alpha10 cRNA. The relative divalent to monovalent cation permeability was high (similar to10) for Ca2+, Ba2+ and Mg2+. Currents evoked by acetylcholine (ACh) were potentiated by either Ca2+ or Ba2+ up to 500 muM 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 muM) than that obtained with 1.8 mM Ca2+ (14.3 muM), suggesting that potentiation by Ca2+ involves changes in the apparent affinity of the alpha9alpha10 receptor for ACh. (C) 2002 Elsevier Science B.V. All rights reserved.