Neuroscience 2000 Abstract
| Presentation Number: | 224.31 |
|---|---|
| Abstract Title: | Estradiol modulates GABA-mediated calcium flux in rat neonatal neurons. |
| Authors: |
Perrot-Sinal, T. S.*1
; Kao, J. P. Y.1,2
; McCarthy, M. M.1
1Department of Physiology, Univ of Maryland School of Medicine, Baltimore, MD 2Medical Biotechnology Center, Univ of Maryland School of Medicine, Baltimore, MD |
| Primary Theme and Topics |
A. Development and Regeneration - 15. Hormones and development |
| Secondary Theme and Topics | A. Development and Regeneration<br />- 9. Neurotransmitter systems and channels |
| Session: |
224. Hormones and development II Poster |
| Presentation Time: | Monday, November 6, 2000 10:00 AM-11:00 AM |
| Location: | Hall G-J |
| Keywords: | Sexual Differentiation, Hypothalamus, Testosterone, Development |
GABA is excitatory in the developing brain due to a positive shift of the chloride equilibrium potential relative to that found in adult neurons. Activation of GABAA receptors depolarizes neurons sufficiently to open L-type voltage-gated Ca2+ channels (J Neurosci 15:5065). During the time when GABA is excitatory, the brain is sexually differentiated under the control of gonadal steroids, primarily estradiol (E2). We reported previously that 10-10M E2 treatment from DIV 1-4, equivalent to embryonic day (ED) 15-ED 18, increased peak levels of free Ca2+ induced by 10μM muscimol in cultured cells imaged on ED 19 (SFN 1999 abstract #197.8). Using a similar hypothalamic culture system generated from ED 15 mixed-sex embryos, we have extended these data by imaging neurons at 8DIV, the equivalent of ED 22 (day of birth; DOB). Cells were loaded with the calcium indicator, Fura-2/AM, and free intracellular Ca2+ was measured. Peak Ca2+ levels were increased (61%) on ED 22 by treating neurons with 10-10M E2 from ED 18-ED 21. Consistent with GABA becoming inhibitory in more mature neurons, 50% fewer neurons responded on ED 22 than responded on ED 19. However, E2 prevented the normal reduction in the number of neurons responding to muscimol on ED 22 (72%-E2 vs. 35%-control). Taken together, our results show that GABA is excitatory, and E2 enhances this excitation, at times that correspond to the ED 18 and DOB testosterone peaks in the male rat. These data, combined with our previous finding that males have significantly higher GABA levels than females on DOB (Neuroscience 90:1471), suggest that E2 mediates sexual differentiation by enhancing excitatory GABA, resulting in increased intracellular Ca2+. Changes in kinetics and/or levels of GABAA receptors, L-type Ca2+ channels and the various ion pumps maintaining the chloride transmembrane potential are under investigation as the mechanism of action of E2. Finally, the regional specificity of this response will be tested by performing experiments in embryonic cortical cultures.
Supported by <I>NIH grant MH52716 to MMM, GM-56481 to JPYK and an NSERC postdoctoral fellowship to TSPS.</I>
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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