Dissociation between Rat Hippocampal CA1 and Dentate Gyrus Cells in Their Response to Corticosterone: Effects on Calcium Channel Protein and Current

Abstract

Stress and corticosterone affect, via glucocorticoid receptors, cellular physiology in the rodent brain. A well-documented example concerns corticosteroid effects on high-voltage activated (L type) calcium currents in the hippocampal CA1 area. We tested whether corticosterone also affects calcium currents in another hippocampal area that highly expresses glucocorticoid receptors, i.e. the dentate gyrus (DG). Remarkably, corticosterone (100 nm, given for 20 min, 1-4.5 hr before recording) did not change high-voltage activated calcium currents in the DG, whereas currents in the CA1 area of the same rats were increased. Follow-up studies revealed that no apparent dissociation between the two areas was observed with respect to transcriptional regulation of calcium channel subunits; thus, in both areas corticosterone increased mRNA levels of the calcium channel-beta4 but not the (alpha) Ca(v)1.2 subunit. At the protein level, however, beta4 and Ca(v)1.2 levels were significantly up-regulated by corticosterone in the CA1 but not the DG area. These data suggest that stress-induced elevations in the level of corticosterone result in a regionally differentiated physiological response that is not simply determined by the glucocorticoid receptor distribution and that the observed regional differentiation may be caused by a gene involved in the translational machinery or in mechanisms regulating mRNA or protein stability.

Unraveling the Time Domains of Corticosteroid Hormone Influences on Brain Activity: Rapid, Slow, and Chronic Modes

“…Slow gene-mediated actions are easier to examine, because these seem to persist in slices prepared from animals earlier exposed to a stressor. For instance, increases in calcium current amplitude were observed several hours after stress exposure and were highly comparable with effects seen in corticosteronetreated slices prepared from naive animals van Gemert et al, 2009). A second drawback inherent to patch-clamp recording is the inevitable perfusion of the intracellular compartment.…”

“…Intracerebroventricular pretreatment with spironolactone dose dependently reversed the corticosterone-induced impairment in retrieval. CORTICOSTEROIDS IN THE BRAIN been exposed to a pulse of corticosterone (van Gemert et al, 2009), although MR activation was shown to be necessary to restrain calcium influx in ADX animals (Karst and Joëls, 2001).…”

“…The increased AHP amplitude probably develops secondary to enhanced calcium influx. The latter pathway is one of the best resolved examples how GR activation can change neuronal function: GR-homodimers bind to DNA of responsive genes (Karst et al, 2000) and transcriptionally up-regulate many genes (Morsink et al, 2006b), including the ␤4 calcium channel subunit (Chameau et al, 2007;van Gemert et al, 2009), resulting in higher ␤4 protein levels (van Gemert et al, 2009) and a higher availability of L-type calcium channels in the membrane (Chameau et al, 2007).…”

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

“…An alternative interpretation may arise from the fact that distinct neuronal subpopulations, even those expressing similar levels of the GR, differ in their response to receptor stimulation (van Gemert et al, 2009). Possibly, the presence of particular GR cofactors are responsible for a cell-type specific response to GR activation (e.g., Grenier et al, 2006;see also below).…”

Social Buffering Prevents Stress-Induced Decreases in Dendritic Length, Branching in Dentate Granule Cells and Hippocampus-Related Memory Performance

“…Likewise, a recent report indicates that corticosterone does not change high-voltage activated calcium currents or calcium channel subunit expression in the dentate gyrus [57]. These lines of evidence suggest that, despite atrophy of the dendritic field of the dentate granule cells, the chemical transmission and basal neuronal activity might not be altered.…”