Ascorbic acid is a positive modulator of the alfa9/alfa10 nicotinic cholinergic receptors.

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

Huerta Grande Cordoba

Congreso; II RCN, Segunda Reunion Conjunta de Neurociencias. Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias; 2010

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

Activity of inhibitory efferent cholinergic neurons projecting from the brainstem and synapsing cochlear hair cells containing a9a10 nicotinic receptors, can ameliorate acoustic trauma. Consequently, compounds that increase a9a10-mediated responses have a potential therapeutic use in noise-induced hearing loss. We have analyzed the effect of ascorbic acid (ASC) in a9a10 injected X. laevis oocytes by two-electrode voltage-clamp recordings. Responses to 10ìM 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%, 3ìM ACh, n=8) than at higher (138±35%, 1mM ACh, n=8) ACh concentrations. No significant changes in the half maximal concentration 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 potentiates a9a10-mediated responses and thus has a potential therapeutic use in noise-induced hearing loss.