Effect of steroids on γ-aminobutyrate-induced currents in cultured rat astrocytes

Abstract

Cultured astrocytes from rat cortex respond to the inhibitory neurotransmitter γ-aminobutyric acid (GABA) by the activation of Cl⁻ channels [Bormann J, Kettenmann H (1988) Proc Natl Acad Sci USA 85:9336–9340]. The glial response shares many pharmacological properties with those mediated by neuronal GABA_A receptors, but differs in its sensitivity to inverse benzodiazepine agonists [Backus KH, Kettenmann H, Schachner M (1988) Glia 1:132–140]. To compare glial GABA receptors further with their neuronal counterparts, we analysed the effect of steroids, which have recently been shown to modulate neuronal GABA_A-receptor-mediated responses, on GABA-induced currents in astrocytes. The agonist allotetrahydrodeoxycorticosterone (THDOC) at concentrations of 100 nM and 1 μM enhanced GABA-evoked (with 10 μM GABA) currents up to 115% and 162.4% of controls respectively. The antagonist dehydroisoandrosterone 3-sulphate (DHEAS) at concentrations of 1 μM, 10 μM and 100 μM depressed GABA-evoked (10 μM) currents to 72%, 42.8% and 21.4% of controls respectively. The steroids were less effective at higher GABA concentrations. 100 μM DHEAS directly elicited a membrane current, while THDOC (1 μM) did not exert any direct response. This study demonstrates that steroids modulate GABA-evoked currents and thus may interfere with any of the functions of glial GABA receptors that are at present under discussion.