Artículo

Calero, C.I.; Vickers, E.; Cid, G.M.; Aguayo, L.G.; von Gersdorff, H.; Calvo, D.J. "Allosteric modulation of retinal GABA receptors by ascorbic acid" (2011) Journal of Neuroscience. 31(26):9672-9682
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Abstract:

Ionotropic GABA 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 goldfish 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 ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, 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 ρ1 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. © 2011 the authors.

Registro:

Documento: Artículo
Título:Allosteric modulation of retinal GABA receptors by ascorbic acid
Autor:Calero, C.I.; Vickers, E.; Cid, G.M.; Aguayo, L.G.; von Gersdorff, H.; Calvo, D.J.
Filiación:Laboratorio de Neurobiología Celular y Molecular, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Universidad de Buenos Aires, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina
The Vollum Institute, Oregon Health and Science University, Portland, OR 97239, United States
Laboratorio de Neurofisiología, Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4030000, Chile
Palabras clave:3 amino 2 (3 carboxypropyl) 6 (4 methoxyphenyl)pyridazinium bromide; 4 aminobutyric acid A receptor; 4 aminobutyric acid C receptor; ascorbic acid; bicuculline methiodide; cysteine loop ligand gated ion channel receptor; histidine; thiol derivative; allosterism; animal cell; article; controlled study; drug determination; drug structure; enzyme regulation; evoked response; goldfish; human; human cell; neuromodulation; neurotransmission; nonhuman; patch clamp; priority journal; protein expression; protein function; retina; retina bipolar ganglion cell; Xenopus laevis
Año:2011
Volumen:31
Número:26
Página de inicio:9672
Página de fin:9682
DOI: http://dx.doi.org/10.1523/JNEUROSCI.5157-10.2011
Título revista:Journal of Neuroscience
Título revista abreviado:J. Neurosci.
ISSN:02706474
CODEN:JNRSD
CAS:3 amino 2 (3 carboxypropyl) 6 (4 methoxyphenyl)pyridazinium bromide, 104104-50-9; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; bicuculline methiodide, 40709-69-1; histidine, 645-35-2, 7006-35-1, 71-00-1; thiol derivative, 13940-21-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v31_n26_p9672_Calero

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Citas:

---------- APA ----------
Calero, C.I., Vickers, E., Cid, G.M., Aguayo, L.G., von Gersdorff, H. & Calvo, D.J. (2011) . Allosteric modulation of retinal GABA receptors by ascorbic acid. Journal of Neuroscience, 31(26), 9672-9682.
http://dx.doi.org/10.1523/JNEUROSCI.5157-10.2011
---------- CHICAGO ----------
Calero, C.I., Vickers, E., Cid, G.M., Aguayo, L.G., von Gersdorff, H., Calvo, D.J. "Allosteric modulation of retinal GABA receptors by ascorbic acid" . Journal of Neuroscience 31, no. 26 (2011) : 9672-9682.
http://dx.doi.org/10.1523/JNEUROSCI.5157-10.2011
---------- MLA ----------
Calero, C.I., Vickers, E., Cid, G.M., Aguayo, L.G., von Gersdorff, H., Calvo, D.J. "Allosteric modulation of retinal GABA receptors by ascorbic acid" . Journal of Neuroscience, vol. 31, no. 26, 2011, pp. 9672-9682.
http://dx.doi.org/10.1523/JNEUROSCI.5157-10.2011
---------- VANCOUVER ----------
Calero, C.I., Vickers, E., Cid, G.M., Aguayo, L.G., von Gersdorff, H., Calvo, D.J. Allosteric modulation of retinal GABA receptors by ascorbic acid. J. Neurosci. 2011;31(26):9672-9682.
http://dx.doi.org/10.1523/JNEUROSCI.5157-10.2011