Estradiol regulates the slow Ca2+-activated K+ current in hippocampal pyramidal neurons.
The slow Ca2+-activated K+ current (sIAHP) was recorded in CA1 pyramidal neurons in hippocampal slices obtained from ovariectomized (OVX) or sham OVX (control) female rats. The sIAHP was significantly larger in cells from OVX rats than in cells from control rats. Superfusion with 5-100 nm 17beta-estradiol (E2) caused a progressive decrease in the sIAHP in cells from OVX rats but not in cells from control rats. In slices from OVX rats injected with 10 microg of E2 24 and 48 hr before they were killed, superfusion with E2 did not modify the sIAHP. In neurons from OVX rats, but not in neurons from control rats, E2 significantly increased both the number of action potentials and the burst duration generated by depolarizing pulses. The inactive isomer 17alpha-estradiol had no effect. The impermeant protein conjugate E2--BSA was as effective as free E2 at decreasing the sIAHP. Ca2+ spikes were also depressed by E2 in neurons from OVX rats, but not in control rats. A decrease in the intracellular Ca2+ signal, correlating with the inhibition of the Ca2+ spike and sIAHP produced by E2, was observed only in neurons from OVX rats. Our results indicate that ovariectomy increases the sIAHP and depresses excitability, whereas bath application or priming with E2 decreases the sIAHP, thus promoting excitability. These effects of E2 on the sIAHP and excitability, which are stereospecific and presumably mediated by membrane-bound receptors, could contribute to the hormonal regulation of synaptic plasticity and epileptiform activity as well as to learning and cognitive abilities dependent on the function of hippocampal neural circuits.
Carrer
Hugo F
HF
Instituto de Investigación Médica M. y M. Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, 5000 Córdoba, Argentina.
Araque
Alfonso
A
Buño
Washington
W
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011959:Receptors, Estradiol / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D024681:Potassium Channels, Calcium-Activated; D011959:Receptors, Estradiol; C043090:estradiol-bovine serum albumin; D012710:Serum Albumin, Bovine; D004958:Estradiol; D011188:Potassium; D002118:Calcium