Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+ currents in rat hippocampal dentate gyrus

N. G. van Gemert*, M. Joels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)

Abstract

Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha 1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the present study, we examined: (i) whether these changes in expression are accompanied by altered Ca2+ currents in rat dentate granule cells recorded on day 22 and (ii) whether treatment with the glucocorticoid receptor antagonist mifepristone during the last 4 days of the stress protocol normalises the putative stress-induced effects. Three weeks of unpredictable stress did not affect Ca2+ current amplitude in dentate granule cells under basal conditions (i.e. after incubation with vehicle solution). However, the sustained Ca2+ current component (which largely depends on the alpha 1C subunit) was significantly increased in amplitude after chronic stress when slices had been treated with corticosterone 1-4 h before recording. These findings suggest that dentate granule cells are exposed to an increased calcium load after exposure to an acute stressor when they have a history of chronic stress, potentially leading to increased vulnerability of the cells. The present results are in line with the molecular data on Ca2+ channel alpha 1C subunit expression. A significant three-way interaction between chronic stress, corticosterone application and mifepristone treatment was found, indicating that the combined effect of stress and corticosterone depends on mifepristone cotreatment. Interestingly, current density (defined as total current divided by capacitance) did not differ between the groups. This indicates that the observed changes in Ca2+ current amplitude could be attributable to changes in cell size.

Original languageEnglish
Pages (from-to)732-741
Number of pages10
JournalJournal of Neuroendocrinology
Volume18
Issue number10
DOIs
Publication statusPublished - Oct-2006
Externally publishedYes

Keywords

  • Ca(2+)current
  • chronic unpredictable stress
  • corticosterone
  • dentate gyrus
  • mifepristone
  • CA3 PYRAMIDAL NEURONS
  • PITUITARY-ADRENAL AXIS
  • ALTERS GENE-EXPRESSION
  • LONG-TERM POTENTIATION
  • DEXAMETHASONE-CRH TEST
  • OPEN-LABEL TRIAL
  • GRANULE CELLS
  • PSYCHOTIC DEPRESSION
  • CALCIUM CURRENTS
  • CORTICOSTEROID ACTIONS

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