Allosteric modulation of retinal GABA receptors by ascorbic acid

Cecilia I. Calero, Evan Vickers, Gustavo Moraga Cid, Luis G. Aguayo, Henrique Von Gersdorff, Daniel J. Calvo

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9672-9682
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number26
DOIs
StatePublished - Jun 29 2011

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GABA Receptors
Ascorbic Acid
gamma-Aminobutyric Acid
GABA-A Receptors
Retina
Cysteine Loop Ligand-Gated Ion Channel Receptors
Ligand-Gated Ion Channels
Goldfish
Presynaptic Terminals
Xenopus laevis
Histidine
Synaptic Transmission
Oxidation-Reduction
Oocytes
Cysteine
GABA-C receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Allosteric modulation of retinal GABA receptors by ascorbic acid. / Calero, Cecilia I.; Vickers, Evan; Cid, Gustavo Moraga; Aguayo, Luis G.; Von Gersdorff, Henrique; Calvo, Daniel J.

In: Journal of Neuroscience, Vol. 31, No. 26, 29.06.2011, p. 9672-9682.

Research output: Contribution to journalArticle

Calero, Cecilia I. ; Vickers, Evan ; Cid, Gustavo Moraga ; Aguayo, Luis G. ; Von Gersdorff, Henrique ; Calvo, Daniel J. / Allosteric modulation of retinal GABA receptors by ascorbic acid. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 26. pp. 9672-9682.
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