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Neurosteroid Modulation of GABA IPSCs is Phosphorylation Dependent

Overview
Journal J Neurosci
Specialty Neurology
Date 2000 Apr 25
PMID 10777770
Citations 55
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Abstract

The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) facilitates GABA(A) receptor-mediated ionic currents via allosteric modulation of the GABA(A) receptor. Accordingly, allopregnanolone caused an increase in the slow decay time constant of spontaneous GABA-mediated IPSCs in magnocellular neurons recorded in hypothalamic slices. The allopregnanolone effect on IPSCs was inhibited by a G-protein antagonist as well as by blocking protein kinase C and, to a lesser extent, cAMP-dependent protein kinase activities. G-protein and protein kinase C activation in the absence of the neurosteroid had no effect on spontaneous IPSCs but enhanced the effect of subsequent allopregnanolone application. These findings together suggest that the neurosteroid modulation of GABA-mediated IPSCs requires G-protein and protein kinase activation, although not via a separate G-protein-coupled steroid receptor.

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References
1.
Bixo M, Andersson A, Winblad B, Purdy R, Backstrom T . Progesterone, 5alpha-pregnane-3,20-dione and 3alpha-hydroxy-5alpha-pregnane-20-one in specific regions of the human female brain in different endocrine states. Brain Res. 1997; 764(1-2):173-8. DOI: 10.1016/s0006-8993(97)00455-1. View

2.
Dunne E, Moss S, Smart T . Inhibition of GABAA receptor function by tyrosine kinase inhibitors and their inactive analogues. Mol Cell Neurosci. 1998; 12(4-5):300-10. DOI: 10.1006/mcne.1998.0717. View

3.
Wang H, Bedford F, Brandon N, Moss S, Olsen R . GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature. 1999; 397(6714):69-72. DOI: 10.1038/16264. View

4.
Poisbeau P, Cheney M, Browning M, Mody I . Modulation of synaptic GABAA receptor function by PKA and PKC in adult hippocampal neurons. J Neurosci. 1999; 19(2):674-83. PMC: 6782188. View

5.
Le Foll F, Louiset E, Castel H, Vaudry H, Cazin L . Electrophysiological effects of various neuroactive steroids on the GABA(A) receptor in pituitary melanotrope cells. Eur J Pharmacol. 1997; 331(2-3):303-11. DOI: 10.1016/s0014-2999(97)01042-x. View