Glucocorticoid actions on synaptic plasma membranes: modulation of dihydropyridine-sensitive calcium channels.
J Steroid Biochem Mol Biol
; 55(2): 185-92, 1995 Nov.
Article
in En
| MEDLINE
| ID: mdl-7495697
ABSTRACT
We have previously shown that glucocorticoids accelerate depolarization-induced 45Ca2+ influx in synaptosomes isolated from rat cerebral cortex, indicating that the steroids may modulate voltage-dependent Ca2+ channels. The present study was undertaken to characterize the biochemical action of glucocorticoids on dihydropyridine-sensitive voltage-dependent Ca2+ channels known to be present in brain synaptosomes. The [3H]dihydropyridine labeled site was used as a marker to determine the levels of functional Ca2+ channels. No effect on equilibrium binding of [3H]PN 200-110 was found when membranes from disrupted synaptosomes were incubated with corticosterone as high as 1 microM. However, when intact synaptosomes were first incubated with corticosterone at 37 degrees C and then disrupted, a significant increase in [3H]PN 200-110 binding was found. Steroid incubation of synaptosomes at 0 degree C was ineffective. It appears that metabolic processes requiring intracellular factors were involved in the steroid action. In examining this possibility, [3H]PN 200-110 binding was activated in disrupted membranes by MgATP and Ca(2+)-calmodulin, and corticosterone was found to enhance the activation in a concentration-dependent manner. [3H]PN 200-110 binding to membranes was also activated by incubation with MgATP and cAMP-dependent protein kinase, but this activation was not enhanced by the steroid. These findings are consistent with the interpretation that the steroid promotes Ca2+ channel activity by enhancing calmodulin-dependent activation of the channels. The action on voltage-dependent Ca2+ channels in synaptic terminals may well be a mechanism whereby glucocorticoids modulate neuronal activity.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
/
Synaptosomes
/
Calcium Channels
/
Cerebral Cortex
/
Glucocorticoids
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
J Steroid Biochem Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
1995
Document type:
Article
Affiliation country: