Effect of steroids on gamma-aminobutyrate-induced currents in cultured
rat astrocytes.
Chvatal A, Kettenmann H
Department of Neurobiology, University of Heidelberg, Federal Republic
of Germany.
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 GABAA 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 GABAA-receptor-mediated responses, on GABA-induced currents in
astrocytes. The agonist allotetrahydrodeoxycorticosterone (THDOC) at concentrations
of 100 nM and 1 microM enhanced GABA-evoked (with 10 microM GABA) currents
up to 115% and 162.4% of controls respectively. The antagonist dehydroisoandrosterone
3-sulphate (DHEAS) at concentrations of 1 microM, and 100 microM depressed
GABA-evoked (10 microM) currents to 72%, 42.8% and 21.4% of controls respectively.
The steroids were less effective at higher GABA concentrations. 100 microM
DHEAS directly elicited a membrane current, while THDOC (1 microM) 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.
