17beta-estradiol benzoate decreases the AHP amplitude in CA1 pyramidal neurons.
Disruption of Ca(2+) homeostasis is hypothesized to mediate several electrophysiological markers of brain aging. Recent evidence indicates that estradiol can rapidly alter Ca(2+)-dependent processes in neurons through nongenomic mechanisms. In the current study, electrophysiological effects of 17beta-estradiol benzoate (EB) on the Ca(2+)-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 Ca(2+) was elevated to increase the AHP amplitude. In aged rats, bath application of EB occluded the ability of the L-channel blocker, nifedipine (10 microM), to attenuate the AHP. The results support a role for EB in modifying hippocampal Ca(2+)-dependent processes in a manner diametrically opposite that observed during aging, possibly through L-channel inhibition.
Kumar
Ashok
A
Department of Molecular and Biomedical Pharmacology, University of Kentucky, College of Medicine, Lexington 40536, USA.
Foster
Thomas C
TC
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010052:Ovariectomy; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004958:Estradiol; C010452:estradiol-17 beta-benzoate; D009543:Nifedipine; D002118:Calcium