Ascorbic acid is a positive modulator of a9a10 nicotinic cholinergic receptors

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

Huerta Grande Cordoba

Congreso; II Reuni¨®n Conjunta de la SAN y TAN, IIRCN; 2010

Ascorbic acid is a positive modulator of a9a10 nicotinic cholinergic receptors.   Juan Carlos Boffi, Carolina Wedemeyer, Eleonora Katz, Daniel Calvo & Ana Bel¨¦n Elgoyhen (elgoyhen@dna.uba.ar).   Instituto de Investigaciones en Ingenier¨ªa Gen¨¦tica y Biolog¨ªa Molecular - INGEBI (CONICET)   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 10¦ÌM acetylcholine (ACh) were potentiated by ASC in a concentration-dependent manner (0.1-30mM ASC). At 3mM ASC, an 81¡À6% (n=7) potentiation was observed. Potentiation was more pronounced at lower (305¡À40%, 3¦ÌM ACh, n=8) than at higher (138¡À35%, 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¡À1, nHill = 0.8¡À0.1, 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.