Present address below: Neuroscience Program, Department of Psychology, Michigan State University, 138 Giltner Hall, East Lansing, MI 48824, USA.
Prolongation and enhancement of γ-aminobutyric acidA receptor mediated excitation by chronic treatment with estradiol in developing rat hippocampal neurons
Article first published online: 15 JUL 2005
European Journal of Neuroscience
Volume 21, Issue 12, pages 3251–3261, June 2005
How to Cite
Nuñez, J. L., Bambrick, L. L., Krueger, B. K. and McCarthy, M. M. (2005), Prolongation and enhancement of γ-aminobutyric acidA receptor mediated excitation by chronic treatment with estradiol in developing rat hippocampal neurons. European Journal of Neuroscience, 21: 3251–3261. doi: 10.1111/j.1460-9568.2005.04175.x
- Issue published online: 15 JUL 2005
- Article first published online: 15 JUL 2005
- Received 14 September 2004, accepted 19 April 2005
- calcium influx;
- excitatory amino acids;
- Sprague–Dawley rats;
- steroid hormones
GABAA receptor activation during brain development is a critical source of excitation. This is due to the positive equilibrium potential for chloride relative to resting membrane potential, resulting in membrane depolarization sufficient to open voltage sensitive calcium channels. The gonadal steroid estradiol has pronounced trophic effects on the developing hippocampus, promoting cell survival and synaptogenesis. In the current study, we investigated the effect of estradiol on GABAA receptor-mediated calcium transients in cultured neonatal hippocampal neurons, from Sprague–Dawley rats, using the calcium sensitive dye, Fura-2-AM. Treatment of hippocampal neurons with physiological levels of estradiol significantly increased the peak amplitude of calcium transients, increased the number of cells responding to the GABAA agonist muscimol with membrane depolarization, and delayed the rate of clearance of free intracellular calcium. These effects were significantly attenuated by pretreatment with the oestrogen receptor antagonist ICI-182,780. This suggests that estradiol, via its action on the oestrogen receptor, prolongs the developmental duration of depolarizing GABA. Estradiol likely maintains GABA-mediated excitation by promoting increased protein levels of the active/phosphorylated form of the chloride cotransporter Na+K+2CL– and L-type voltage sensitive calcium channels containing the α1C subunit. We propose that a component of the trophic effects of estradiol on hippocampal development results from enhanced calcium influx subsequent to GABAA receptor activation.