EFFECT OF STEROIDS ON GAMMA-AMINOBUTYRATE-INDUCED CURRENTS IN CULTURED RAT ASTROCYTES

Cultured astrocytes from rat cortex respond to the inhibitory neurotransmitter gamma-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 allotetrahydrodeoxycortico-sterone (THDOC) at concentrations of 100 nM and 1-mu-M enhanced GABA-evoked (with 10-mu-M GABA) currents up to 115% and 162.4% of controls respectively. The antagonist dehydroisoandrosterone 3-sulphate (DHEAS) at concentrations of 1-mu-M, 10-mu-M and 100-mu-M depressed GABA-evoked (10-mu-M) currents to 72%, 42.8% and 21.4% of controls respectively. The steroids were less effective at higher GABA concentrations. 100-mu-M DHEAS directly elicited a membrane current, while THDOC (1-mu-M) 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.