title: Acute stress increases calcium current amplitude in rat hippocampus: temporal changes in physiology and gene expression.
abstract: Activation of hippocampal glucocorticoid receptors in vitro increases calcium current amplitude through a process requiring DNA binding of receptor homodimers. We here investigated (i). whether similar increased calcium currents also occur following in vivo glucocorticoid receptor activation due to stress and (ii). if so, whether this can be explained by increased expression of calcium channel subunits. Rats were exposed to a novelty stress; some of the animals were pretreated with a glucocorticoid receptor antagonist. In subsequently prepared hippocampal slices, calcium currents were recorded from identified CA1 pyramidal neurons, after which RNA was collected, linearly amplified and hybridized with cDNA clones. Glucocorticoid receptor activation due to novelty exposure was associated with large total peak calcium currents and high-threshold noninactivating currents. Low-threshold calcium currents were not affected. Large total peak and noninactivating current amplitudes were also seen when animals received a more severe stressor, i.e. additional ether exposure. In the stressed groups, the total peak and high-threshold calcium current gradually increased with time resulting in a significant enhancement at >or=3 h after stress exposure. In the same cells, the summated (relative) RNA expression of various alpha1 calcium channel subunits was only transiently enhanced, prior to the functional changes. These data indicate that in vivo activation of glucocorticoid receptors due to stress gradually increases specific calcium current components. Prior to the functional change, increased expression of calcium channel subunits was observed, suggesting that the enhanced function could be explained by transcriptional regulation of the channels.
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. joels@science.uva.nl
authors.forename: M
authors.initials: M
authors.lastname: Joëls
authors.forename: E
authors.initials: E
authors.lastname: Velzing
authors.forename: S
authors.initials: S
authors.lastname: Nair
authors.forename: J M
authors.initials: JM
authors.lastname: Verkuyl
authors.forename: H
authors.initials: H
authors.lastname: Karst
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004553:Electric Conductivity; D004986:Ether / Q000633:toxicity; D015870:Gene Expression / Q000502:physiology*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D013312:Stress, Physiological / Q000139:chemically induced / Q000235:genetics*; D013997:Time Factors
chemical_list: D064026:Calbindins; D015220:Calcium Channels; D006727:Hormone Antagonists; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D064030:S100 Calcium Binding Protein G; D004986:Ether; D015735:Mifepristone; D012313:RNA; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium