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

NOELIA WEISSTAUB,; ELEONORA KATZ,; DOUG VETTER,; JIM BOULTER; ANA BELÉN ELGOYHEN

HEARING RESEARCH.

Año: 2002 p. 122 - 135

0378-5955

The native cholinergic receptor that mediates synaptic transmission between olivocochlear fibers and outer hair cells of thecochlea is permeable to Ca2þ and is thought to be composed of both the K9 and the K10 cholinergic nicotinic subunits. The aim ofthe present work was to study the permeability of the recombinant K9K10 nicotinic acetylcholine receptor to Ca2þ, B a2þ and Mg2þand its modulation by these divalent cations. Experiments were performed, by the two-electrode voltage-clamp technique, inXenopus laevis oocytes injected with K9 and K10 cRNA. The relative divalent to monovalent cation permeability was high (V10)for Ca2þ, B a2þ and Mg2þ. Currents evoked by acetylcholine (ACh) were potentiated by either Ca2þ or Ba2þ up to 500 WM butwere blocked by higher concentrations of these cations. Potentiation by Ca2þ was voltage-independent, whereas blockage wasstronger at hyperpolarized than at depolarized potentials. Mg2þ did not potentiate but it blocked ACh-evoked currents (IC50 =0.38 mM). In the absence of Ca2þ, the EC50 for ACh was higher (48 WM) than that obtained with 1.8 mM Ca2þ (14.3 WM),suggesting that potentiation by Ca2þ involves changes in the apparent affinity of the K9K10 receptor for ACh.