Novel mechanism for non-genomic action of 17 beta-oestradiol on kainate-induced currents in isolated rat CA1 hippocampal neurones.

Abstract

1. Using whole-cell voltage-clamp recordings of dissociated hippocampal CA1 neurones, we demonstrated that 17 beta-oestradiol rapidly potentiates kainate-induced currents when applied either to the outside or the inside of the neurone. However, when the steroid was conjugated to bovine serum albumin (E2-BSA), application to either the extracellular plasma membrane (E2-BSAout) or the cytosolic side of the cell (E2-BSAin) had no observable effect on kainate-induced currents. However, when applied stimultaneously to both sides of the plasma membrane, E2-BSA potentiated kainate-induced currents. 2. Application of E2-BSAout and GTP gamma S(in) potentiated kainate-induced currents. The potentiation of kainate-induced currents by 17 beta-oestradiol was occluded by cholera toxin pretreatment and appeared to be pertussis toxin insensitive. 3. E2-BSAin prolonged the effect of 8-bromoadenosine 3',5' cyclic monophosphate (8-bromo-cAMP) on kainate-induced currents. The recovery from the 8-bromo-cAMP response was found to be a function of the concentration of E2-BSAin. The application of ATP gamma S(in) occluded the effect of 17 beta-oestradiol. 4. These results suggest that the non-genomic action of 17 beta-oestradiol in the potentiation of kainate-induced currents is mediated via an action on Gs protein-coupled receptors. This operates in concert with an internal action of 17 beta-oestradiol on a cAMP-dependent phosphorylation.