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The Journal of Neuroscience, May 1, 2000, 20(9):3067-3075

Neurosteroid Modulation of GABA IPSCs Is Phosphorylation Dependent

András Fáncsik1, David M. Linn1, and Jeffrey G. Tasker1, 2

1 Department of Cell and Molecular Biology and 2 Neuroscience Program, Tulane University, New Orleans, Louisiana 70118-5698

The neurosteroid 3alpha -hydroxy-5alpha -pregnan-20-one (allopregnanolone) facilitates GABAA receptor-mediated ionic currents via allosteric modulation of the GABAA 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.

Key words: hypothalamus; neurosteroid; progestin; allopregnanolone; kinase; phosphorylation; GABAA receptor; G-proteins; whole-cell recording

Copyright © 2000 Society for Neuroscience  0270-6474/00/2093067-09$05.00/0


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