DIFFERENTIAL MODULATION BY SULFHYDRYL REDOX AGENTS AND GLUTATHIONE OFGABA-EVOKED AND GLYCINE-EVOKED CURRENTS IN RAT RETINAL GANGLION-CELLS

Some areas of the mammalian CNS, such as the retina, contain not one b ut two fast inhibitory neurotransmitter systems whose actions are medi ated by GABA and glycine. Each inhibitory receptor system is encoded b y a separate gene family and has a unique set of agonists and antagoni sts. Therefore, in rat retinal ganglion cells we were surprised to fin d that a single agent, extracellular glutathione, was capable of modul ating currents activated by either GABA(A) or glycine receptor stimula tion. Both oxidized and reduced glutathione influence inhibitory neuro transmission in a manner similar to that of the sulfhydryl redox agent s dithiothreitol (DTT) and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB ). Remarkably, the actions of glutathione are diametrically opposed on the GABA(A) and glycine systems. In whole-cell recordings of single r etinal ganglion cells with patch pipettes, reduced glutathione enhance s GABA-evoked currents but decreases glycine-evoked currents. These fi ndings suggest that endogenous redox agents, such as glutathione, may constitute a novel modulatory system for the differential regulation o f inhibitory neurotransmission in the mammalian retina.