Allosteric modulation of retinal GABA receptors by ascorbic acid

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 pr...

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Autores principales:	Calero, C.I., Vickers, E., Cid, G.M., Aguayo, L.G., von Gersdorff, H., Calvo, D.J.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_02706474_v31_n26_p9672_Calero
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_02706474_v31_n26_p9672_Calero
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spelling	todo:paper_02706474_v31_n26_p9672_Calero2023-10-03T15:14:42Z Allosteric modulation of retinal GABA receptors by ascorbic acid Calero, C.I. Vickers, E. Cid, G.M. Aguayo, L.G. von Gersdorff, H. Calvo, D.J. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02706474_v31_n26_p9672_Calero
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Calero, C.I. Vickers, E. Cid, G.M. Aguayo, L.G. von Gersdorff, H. Calvo, D.J.
author_facet	Calero, C.I. Vickers, E. Cid, G.M. Aguayo, L.G. von Gersdorff, H. Calvo, D.J.
author_sort	Calero, C.I.
title	Allosteric modulation of retinal GABA receptors by ascorbic acid
title_short	Allosteric modulation of retinal GABA receptors by ascorbic acid
title_full	Allosteric modulation of retinal GABA receptors by ascorbic acid
title_fullStr	Allosteric modulation of retinal GABA receptors by ascorbic acid
title_full_unstemmed	Allosteric modulation of retinal GABA receptors by ascorbic acid
title_sort	allosteric modulation of retinal gaba receptors by ascorbic acid
url	http://hdl.handle.net/20.500.12110/paper_02706474_v31_n26_p9672_Calero
work_keys_str_mv	AT caleroci allostericmodulationofretinalgabareceptorsbyascorbicacid AT vickerse allostericmodulationofretinalgabareceptorsbyascorbicacid AT cidgm allostericmodulationofretinalgabareceptorsbyascorbicacid AT aguayolg allostericmodulationofretinalgabareceptorsbyascorbicacid AT vongersdorffh allostericmodulationofretinalgabareceptorsbyascorbicacid AT calvodj allostericmodulationofretinalgabareceptorsbyascorbicacid
_version_	1782029638948618240

Allosteric modulation of retinal GABA receptors by ascorbic acid

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