INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Allosteric modulation of retinal GABA receptors by ascorbic acid.
Autor/es:
CALERO CI; VICKERS E; MORAGA-CID G; AGUAYO L; VON GERSDORFF H; CALVO DJ
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Año: 2011 vol. 1 p. 1000 - 10000
ISSN:
0270-6474
Resumen:
Ionotropic ã-aminobutyric acid receptors (GABAA And GABAC)belong to the cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina,mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However,the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA,and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA-puff evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ñ1 GABAC receptors expressed in Xenopus oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereospecific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two cys-loop cysteines and histidine 141, all located in the ñ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally,we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.