Conductance of GABAA channels activated by pentobarbitone in hippocampal neurons from newborn rats.
Neurons were obtained from the CA1 region of the hippocampus of newborn rats and maintained in culture. Channels were activated by pentobarbitone in cell-attached, inside-out or outside-out patches, normally by applying pentobarbitone in flowing bath solution. Currents were outwardly rectifying and blocked by bicuculline, properties of GABAA channels in these cells. Maximum channel conductance increased as pentobarbitone concentration was increased to 500 microM but conductance then decreased as pentobarbitone concentration was raised further. The best fit of a Hill-type equation to the relationship between maximum channel conductance and pentobarbitone concentration (up to 500 microM) gave an EC50 of 41 microM, a maximum conductance of 36 pS and a Hill coefficient of 1.6. Bicuculline decreased the maximum conductance of the channels activated by pentobarbitone, with an IC50 of 224 microM. Diazepam increased channel conductance, with a maximum effect being obtained with 1 microM diazepam. Diazepam (1 microM) decreased the EC50 of the pentobarbitone effect on channel conductance from 41 microM to 7.2 microM and increased maximum conductance to 72 pS. We conclude that GABAA channel conductance is related to the concentration of the allosteric agonist pentobarbitone.
Eghbali
Mansoureh
M
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
Birnir
Bryndis
B
Gage
Peter W
PW
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D003975:Diazepam / Q000494:pharmacology; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D003975:Diazepam; D001640:Bicuculline