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

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Abstract
1 Using whole-cell voltage-clamp recordings of dissociated hippocampal CA1 neurones, we demonstrated that 17β-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 GTPγSin potentiated kainate-induced currents. The potentiation of kainate-induced currents by 17β-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 ATPγSin occluded the effect of 17β-oestradiol. 4 These results suggest that the non-genomic action of 17β-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 17β-oestradiol on a cAMP-dependent phosphorylation.