NEUROSTEROIDS ACT ON RECOMBINANT HUMAN GABA-A RECEPTORS

The endogenous steroid metabolites 3α,21dihydroxy-5α-pregnan-20-one and 3α-hydroxy-5α-pregnan-20-one potentiate GABA-activated Cl- currents recorded from a human cell line transfected with the β1, α1β1, and α1β1γ2 combinations of human GABAA receptor subunits. These steroids are active at nanomolar concentrations in potentiating GABA-activated Cl- currents and directly elicit bicuculline-sensitive C- currents when applied at micromolar concentrations. The potentiating and direct actions of both steroids were expressed with every combination of subunits tested. However, an examination of single-channel currents recorded from outside-out patches excised from these transfected cells suggests that despite the common minimal structural requirements for expressing steroid and barbiturate actions, the mechanism of GABAA receptor modulation by these pregnane steroids may differ from that of barbiturates. © 1990.