Corticosterone impairs cultured hippocampal neurons and facilitates Ca2+ influx through voltage-dependent Ca2+ channel

Citation
Jz. Zhou et al., Corticosterone impairs cultured hippocampal neurons and facilitates Ca2+ influx through voltage-dependent Ca2+ channel, ACT PHAR SI, 21(2), 2000, pp. 156-160
Citations number
16
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ACTA PHARMACOLOGICA SINICA
ISSN journal
02539756 → ACNP
Volume
21
Issue
2
Year of publication
2000
Pages
156 - 160
Database
ISI
SICI code
0253-9756(200002)21:2<156:CICHNA>2.0.ZU;2-S
Abstract
AIM: To investigate the effect of corticosterone (Cor) on the viability of cultured hippocampal neurons as well as voltage-dependent Ca2+ channel (VDC C) on the membrane of the hippocampal neurons. METHODS: The primary culture d hippocampal neurons were prepared and the viability of hippocampal neuron s was determined by MTT assays. Inward Ca2+ currents of VDCC on the membran e of the hippocampal neurons were measured with the whole-cell patch-clamp technique. RESULTS: Treatment with Cor concentration-dependently reduced th e survival of hippocampal neurons. The IC50 of Cor was 3.2 mu mol L-1. Neur ons from cerebral cortex were affected only by high concentrations of Cor ( 10 mu mol.L-1 and 0.1 mmol.L-1) with the IC50, 85 mu mol.L-1, 20 times larg er than the former. Whole-cell patch-clamp experiment showed that Cor (1 mu mol.L-1 -0.1 mu mol.L-1) sprayed to the surface of the hippocampal neurons instantly facilitated Ca2+ influx through VDCC with the maximal elevation of 53 %, 191 %, and 84 % above the baseline respectively and this effect wa s shown to be concentration-independent. In addition, changing the membrane potentials from - 40 mV to - 10 mV did not affect the facilitating effect of Cor on the Ca2+ influx, indicating that Cor-induced Ca2+ influx was memb rane potential-independent. CONCLUSION: Cor markedly facilitated Ca2+ influ x into the hippocampal neurons, which may be one of the important mechanism s underlying the neurotoxicity of Cor to hippocampus.