Novel mechanism for non-genomic action of 17 beta-oestradiol on kainate-induced currents in isolated rat CA1 hippocampal neurones.
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.
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Department of Physiology, University of Texas Southwestern Medical Center at Dallas 75235, USA.
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D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D004958:Estradiol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine
D018690:Excitatory Amino Acid Agonists; D007473:Ion Channels; D009498:Neurotoxins; D012710:Serum Albumin, Bovine; D004958:Estradiol; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007608:Kainic Acid