Corticosterone impairs cultured hippocampal neurons and facilitates Ca2+ influx through voltage-dependent Ca2+ channel.
OBJECTIVE
To investigate the effect of corticosterone (Cor) on the viability of cultured hippocampal neurons as well as voltage-dependent Ca2+ channel (VDCC) on the membrane of the hippocampal neurons.


METHODS
The primary cultured hippocampal neurons were prepared and the viability of hippocampal neurons was determined by MTT assays. Inward Ca2+ currents of VDCC on the membrane of the hippocampal neurons were measured with the whole-cell patch-clamp technique.


RESULTS
Treatment with Cor concentration-dependently reduced the survival of hippocampal neurons. The IC50 of Cor was 3.2 mumol.L-1. Neurons from cerebral cortex were affected only by high concentrations of Cor (10 mumol.L-1 and 0.1 mmol.L-1) with the IC50, 85 mumol.L-1, 20 times larger than the former. Whole-cell patch-clamp experiment showed that Cor (1 mumol.L(-1)-0.1 mmol.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 was 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 membrane potential-independent.


CONCLUSIONS
Cor markedly facilitated Ca2+ influx into the hippocampal neurons, which may be one of the important mechanisms underlying the neurotoxicity of Cor to hippocampus.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. zhoujz@nic.bmi.ac.cn
J Z
JZ
Zhou
J Q
JQ
Zheng
Y X
YX
Zhang
J H
JH
Zhou
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003345:Corticosterone / Q000633:toxicity*; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D015220:Calcium Channels; D002118:Calcium; D003345:Corticosterone