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Updated: May 31, 2026
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Glutamate and Hypoxia as a Stress Model for the Isolated Perfused Vertebrate Retina
Published on: March 22, 2015
Allosteric modulation of retinal GABA receptors by ascorbic acid.
Cecilia I Calero1, Evan Vickers, Gustavo Moraga Cid
1Laboratorio de Neurobiología Celular y Molecular, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina.
Summary
Ascorbic acid enhances the function of GABA(A) and GABA(C) receptors in the retina. This suggests ascorbic acid may boost GABAergic neurotransmission in the central nervous system.
Area of Science:
- Neuroscience
- Neurophysiology
- Biochemistry
Background:
- Ionotropic GABA receptors, including GABA(A) and GABA(C) types, are crucial ligand-gated ion channels.
- GABA(C) receptors are abundant in the retina, particularly at bipolar cell axon terminals.
- Ascorbic acid, a potent endogenous antioxidant, is present at high concentrations in the retina.
Purpose of the Study:
- To investigate the effect of ascorbic acid on retinal GABA(A) and GABA(C) receptor function.
- To determine if ascorbic acid modulates GABAergic neurotransmission in the central nervous system.
Main Methods:
- Patch-clamp recordings were performed on goldfish retinal slices and Xenopus laevis oocytes expressing GABA receptors.
- Chemical modification studies targeted sulfhydryl groups to identify key amino acid residues involved in modulation.
- GABA-evoked currents and inhibitory postsynaptic currents (IPSCs) were measured.
Main Results:
- Ascorbic acid significantly enhanced GABA(C) receptor-mediated currents in retinal bipolar cell terminals.
- GABA puff-evoked currents showed rundown in the absence of ascorbic acid, but were potentiated by it.
- Ascorbic acid potentiated GABA-evoked currents in homomeric ρ(1) GABA(C) receptors in a concentration-dependent, stereospecific, reversible, and voltage-independent manner.
- Specific residues in the ρ(1) subunit (Cys-loop cysteines and His141) are critical for ascorbic acid modulation.
- Retinal GABA(A) IPSCs and heterologously expressed GABA(A) receptor currents were also augmented by ascorbic acid.
Conclusions:
- Ascorbic acid potentiates the function of both GABA(A) and GABA(C) receptors in the retina.
- Ascorbic acid acts as a positive allosteric modulator of retinal GABA receptors.
- Ascorbic acid may serve as an endogenous potentiator of GABAergic neurotransmission in the central nervous system.
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