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

Acta Pharmacol Sin. 2000 Feb;21(2):156-60.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / toxicity*
  • Biological Transport, Active / drug effects
  • Calcium / metabolism*
  • Calcium Channels / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Corticosterone / toxicity*
  • Embryo, Mammalian
  • Hippocampus / cytology*
  • Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Calcium Channels
  • Calcium
  • Corticosterone