Pregnenolone sulfate antagonizes GABAA receptor-mediated currents via a reduction of channel opening frequency.
Our previous study showed antagonism of GABAA receptor-mediated whole-cell currents by pregnenolone sulfate (PS). Here, the effects of PS, picrotoxin (PTX) and pentobarbital (PB) were tested on GABA-activated single Cl- channels recorded from membrane patches of rat cortical neurons in primary cultures. PS and PTX selectively decreased the opening frequency of the channels, while PB increased mean open time and burst duration without affecting opening frequency. It is suggested that PS and PTX may antagonize GABAA receptor function through the same mechanism and/or the same binding site.
Mienville
J M
JM
FIDIA-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington 20007.
Vicini
S
S
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology*; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D010424:Pentobarbital; D010852:Picrotoxin; D011284:Pregnenolone; D011963:Receptors, GABA-A; C018370:pregnenolone sulfate