Ascorbic acid is a positive modulator of a9a10 nicotinic cholinergic receptors

BOFFI JC; WEDEMEYER C; CALVO DJ; KATZ E; ELGOYHEN AB

Huerta Grande, Córdoba, Argentina

Congreso; Segunda Reunión Conjunta de la Sociedad Argentina de Neurociencias (SAN) y el Taller Argentino de Neurociencias (TAN); 2010

Activity of inhibitory efferent cholinergic neurons projecting from the brainstem and synapsing cochlear hair cells containing á9á10 nicotinic receptors, can ame- liorate acoustic trauma. Consequently, compounds that increase á9á10-mediated responses have a potential therapeutic use in noise-induced hearing loss. We have analyzed the effect of ascorbic acid (ASC) in á9á10 injected X. laevis oocytes by two-electrode voltage-clamp recordings. Responses to 10µM acetylcholine (ACh) were potentiated by ASC in a concentration-dependent manner (0.1-30mM ASC). At 3mM ASC, an 81±6% (n=7) potentiation was observed. Potentiation was more pronounced at lower (305±40%, 3µM ACh, n=8) than at higher (138±35%, 1mM ACh, n=8) ACh concentrations. No significant changes in the half maximal con- centration of ACh and Hill coefficients were observed at 3mM ASC (EC50 = 18±1, nHill = 0.8±0.1, n=5-9). The ASC oxidized form, dihidroascorbate, had no effect on ACh-evoked responses at a 3mM concentration, suggesting that the reduced form of ASC is the active compound. Altogether, our results show that ASC po- tentiates á9á10-mediated responses and thus has a potential therapeutic use in noise-induced hearing loss.