Enhancement of the excitatory actions of GABA by barbiturates and benzodiazepines.
Whole cell recordings from hippocampal CA1 pyramidal neurons using electrode chloride concentrations of 12-80 mM demonstrated that the effect of synaptic activation of GABAA receptors was dependent on the transmembrane chloride gradient. When the chloride reversal potential was positive to action potential threshold, GABAA receptor activation was excitatory, and anticonvulsant barbiturates and benzodiazepines enhanced this excitation. Enhancement of GABAergic excitation of interneurons may contribute to the efficacy of these drugs, while enhancement of GABAergic excitation of principal neurons may be an important mechanism of failure, such as occurs in the treatment of neonatal seizures.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D001569:Benzodiazepines; D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001463:Barbiturates; D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D007473:Ion Channels; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid