Neurosteroid modulation of GABA IPSCs is phosphorylation dependent.
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.
Fáncsik
A
A
Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118-5698, USA.
Linn
D M
DM
Tasker
J G
JG
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011280:Pregnanolone / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D018757:GABA Modulators; D011963:Receptors, GABA-A; D011280:Pregnanolone; D011494:Protein Kinases; D019204:GTP-Binding Proteins