An intracellular redox sensor for reactive oxygen species at theM3‐M4 linker ofGABAAρ1receptors

• DOI: 10.1111/bph.12581
• Publication Date: 2014-01-16T03:46:58Z
• Authors: Andrea N Beltrán ...; Javier Gasulla; Daniel J Calvo
• Keywords: GABAA-rho receptor; Gamma-Aminobutyric Acid

Reactive oxygen species (ROS) are normally involved in cell oxidative stress but also play a role as cellular messengers redox signalling; for example, modulating the activity of neurotransmitter receptors and ion channels. However, direct actions ROS on GABAA were not previously demonstrated. In present work, we studied effects ρ1 receptor function.GABAA expressed oocytes GABA-evoked responses electrophysiologically recorded presence or absence ROS. Chemical protection cysteines by selective sulfhydryl reagents site-directed mutagenesis studies used to identify protein residues actions.GABAA receptor-mediated significantly enhanced concentration-dependent reversible manner H₂O₂. Potentiating attenuated free radical scavenger, lipoic acid an inhibitor Fenton reaction, deferoxamine. Each subunit contains only three cysteine residues, two extracellular at Cys-loop (C¹⁷⁷ C¹⁹¹) one intracellular (C³⁶⁴) M3-M4 linker. Mutant which C³⁶⁴ was exchanged alanine completely insensitive modulation, implying that this site, rather than Cys-loop, is essential modulation.Our results show function sensor actions.