Allopregnanolone, known so far to act as a γ-aminobutyric acid (GABA) agonist, allosterically decreased the affinity of the GABA agonist muscimol for recombinant α1β2γ2 and α6β2γ2 GABAA receptors. Pregnenolone sulfate, a GABA antagonist, had a similar effect. Both of these neuroactive steroids also reduced the time constant of desensitization (τ) of GABA-induced chloride currents. The effect on desensitization was demonstrated for native receptors of hypothalamic neurons as well as for the recombinant GABAA receptors. Hence neuroactive steroids may differentially modulate distinct assemblies of GABAA receptors and thus induce a more subtle modulation of GABAergic synaptic transmission than previously thought possible.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Molecular Biology