Negative modulation of the GABAA ρ1 receptor function by l-cysteine
Andrea N Beltrán González1, Florencia Vicentini1, Daniel J Calvo1
1Laboratorio de Neurobiología Celular y Molecular, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Journal of Neurochemistry
|October 13, 2017
Summary
L-cysteine antagonizes GABAergic neurotransmission by inhibiting GABAA ρ1 receptors. This study reveals L-cysteine acts as a competitive antagonist, impacting neuronal signaling in the central nervous system.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- L-cysteine, a sulfur-containing amino acid, has dual roles in the central nervous system, acting as both neuroprotective and potentially excitotoxic.
- While L-cysteine's effects on various ion channels are known, its impact on GABAergic neurotransmission remained unexplored.
Purpose of the Study:
- To investigate the effects of L-cysteine on homomeric GABAA ρ1 receptors, which mediate tonic γ-aminobutyric acid (GABA) responses in retinal neurons.
- To determine the mechanism by which L-cysteine modulates GABAA ρ1 receptor activity.
Main Methods:
- GABAA ρ1 receptors were expressed in Xenopus laevis oocytes.
- GABA-evoked chloride currents were recorded using two-electrode voltage-clamp in the presence and absence of L-cysteine.
- The effect of L-cysteine was assessed under varying GABA concentrations and with chemical protection of sulfhydryl groups.
Main Results:
- L-cysteine demonstrated a dose-dependent, reversible, and voltage-independent antagonism of GABAA ρ1 receptor-mediated responses.
- L-cysteine shifted GABA concentration-response curves to the right without altering the maximal response, suggesting competitive antagonism.
- Inhibition by L-cysteine was unaffected by N-ethyl maleimide, indicating redox-independent action.
Conclusions:
- L-cysteine acts as a competitive antagonist at GABAA ρ1 receptors.
- The inhibitory effects of L-cysteine on these receptors are not mediated by redox modulation.
- These findings elucidate a novel role for L-cysteine in modulating inhibitory neurotransmission.
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