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

AIM

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.

CONCLUSION

Cor markedly facilitated Ca2+ influx into the hippocampal neurons, which may be one of the important mechanisms underlying the neurotoxicity of Cor to hippocampus.