17β-estradiol benzoate decreases the AHP amplitude in CA1 pyramidal neurons

Disruption of Ca2+ homeostasis is hypothesized to mediate several electrophysiological markers of brain aging. Recent evidence indicates that estradiol can rapidly alter Ca2+-dependent processes in neurons through nongenomic mechanisms. In the current study, electrophysiological effects of 17beta-estradiol benzoate (EB) on the Ca2+-activated afterhyperpolarization (AHP) were investigated using intracellular sharp electrode recording in hippocampal slices from ovariectomized Fischer 344 female rats. The AHP amplitude was enhanced in aged (22-24 mo) compared with young (5-8 mo) rats and direct application of EB (100 pM) reduced the AHP in aged rats. The age-related difference was due, in part, to the increased AHP amplitude of aged animals, since an EB-mediated decrease in the AHP could be observed in young rats when the extracellular Ca2+ was elevated to increase the AHP amplitude. In aged rats, bath application of EB occluded the ability of the L-channel blocker, nifedipine (10 muM), to attenuate the AHP. The results support a role for EB in modifying hippocampal Ca2+-dependent processes in a manner diametrically opposite that observed during aging, possibly through L-channel inhibition.