Alcohol modulation of cloned GABAA receptor-channel complex expressed in human kidney cell lines.
The effects of n-octanol on GABA-induced currents were examined on the alpha 1 beta 2 gamma 2s and alpha 1 beta 2 combinations of GABAA receptor subunits expressed in a human kidney cell line (HEK 293), using the whole-cell variation of the patch clamp technique. The EC50 of the GABA dose-response curve for the alpha 1 beta 2 combination was lower than that for the alpha 1 beta 2 gamma 2s combination. n-Octanol at 100 microM augmented the GABA-induced currents in a dose-dependent manner, decreasing the EC50 of the GABA dose-response curve without affecting the maximal response. The magnitude of n-octanol potentiation was nearly the same in both combinations. In contrast, a benzodiazepine agonist, chlordiazepoxide, augmented the currents of the alpha 1 beta 2 gamma 2s combination only. We conclude that the potentiation of GABAA receptor-mediated currents by a long carbon chain n-alcohol does not require the gamma 2 subunit.
Kurata
Y
Y
Department of Pharmacology, Northwestern University, Medical School, Chicago, IL 60611.
Marszalec
W
W
Hamilton
B J
BJ
Carter
D B
DB
Narahashi
T
T
D020003:1-Octanol; D002460:Cell Line; D002707:Chlordiazepoxide / Q000494:pharmacology; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000442:Octanols / Q000494:pharmacology*; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D007473:Ion Channels; D000442:Octanols; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; D020003:1-Octanol