Desensitization and noncompetitive blockade of GABAA receptors in ventral midbrain neurons by a neurosteroid dehydroepiandrosterone sulfate.
Dehydroepiandrosterone sulfate (DHEAS) blocked the GABAA receptor noncompetitively in neurons grown in primary culture from the ventral midbrains of fetal rats. The apparent dissociation constant for this blockade was 4.5 microM, and one molecule of DHEAS was sufficient to block the receptor. The affinity of the blocked receptor for GABA was diminished by about one half. The findings that the DHEAS caused no rectification of chloride currents and that it did not shorten the durations of open ion channels indicated that DHEAS did not act by occluding open ion channels. Neither did it diminish their conductance. DHEAS accelerated desensitization in at least one population of receptors, diminished the amplitudes of inhibitory postsynaptic currents, and shortened their decay time constants in a concentration dependent manner.
Spivak
C E
CE
Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224.
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D004594:Electrophysiology; D005333:Fetus / Q000378:metabolism; D018756:GABA Antagonists; D007473:Ion Channels / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D007473:Ion Channels; D018079:Receptors, GABA; D003687:Dehydroepiandrosterone; D005680:gamma-Aminobutyric Acid; D019314:Dehydroepiandrosterone Sulfate