17-BETA-ESTRADIOL POTENTIATES KAINATE-INDUCED CURRENTS VIA ACTIVATIONOF THE CAMP CASCADE

Evidence for nongenomic actions of steroids is now coming from a varie ty of fields of steroid research. Mechanisms of steroid action are bei ng studied with regard to the membrane receptors and the activation of second messengers. The present study investigated the mechanism for t he rapid effect of estrogen on acutely dissociated hippocampal CA1 neu rons by using the whole-cell, voltage-clamp recording. Under the perfo rated patch configuration, 17 beta-estradiol potentiated kainate-induc ed currents in 38% of tested neurons. The potentiation was stereospeci fic, rapid in onset, and reversible after the removal of the steroid. Dose-response curves show that the potentiation by 17 beta-estradiol w as evident at a concentration as low as 10 nM and saturated at 10 mu M . 17 beta-Estradiol did not affect the kinetics (i.e., affinity and co operativity) and reversal potential of kainate-induced currents. This suggests that the potentiation did not result from direct interaction with kainate receptors nor the activation of ion channels other than k ainate receptor-channels. The potentiation by 17 beta-estradiol was si milar to the enhancement of kainate-induced currents evoked by 8-bromo -cAMP, and was modulated by an inhibitor of phosphodiesterase (IBMX). The estrogen potentiation was blocked by a specific blocker of PKA (Rp -cAMPS). Under standard recording configuration, the effect was signif icantly affected by intracellular perfusing with GDP-beta-S or GTP-gam ma-S. The data suggest that the potentiation of kainate-induced curren ts by 17 beta-estradiol was likely a G-protein(s) coupled, cAMP-depend ent phosphorylation event. By involvement of this nongenomic mechanism , estrogen may play a role in the modulation of excitatory synaptic tr ansmission in the hippocampus.