Effects of propofol on GABAA channel conductance in rat-cultured hippocampal neurons.
Channels were activated, in ripped-off patches from rat-cultured hippocampal neurons, by propofol alone, propofol plus 0.5 microM GABA (gamma-aminobutyric acid) or GABA alone. The propofol-activated currents were chloride-selective, showed outward-rectification and were enhanced by 1 microM diazepam. The maximum propofol-activated channel conductance increased with propofol concentration from less than 15 pS (10 microM) to about 60 pS (500 microM) but decreased to 40 pS in 1 mM propofol. Fitting the data from 10 to 500 microM propofol with a Hill-type equation gave a maximum conductance of 64 pS, an EC50 value of 32 microM and a Hill coefficient of 1.1. Addition of 0.5 microM GABA shifted the propofol EC50 value to 10 microM and increased the maximum channel conductance to about 100 pS. The Hill coefficient was 0.8. The maximum channel conductance did not increase further when 1 microM diazepam was added together with a saturating propofol concentration and GABA. The results are compared to effects other drugs have on GABAA channels conductance.
Eghbali
Mansoureh
M
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, Canberra, Australia
Gage
Peter W
PW
Birnir
Bryndis
B
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018118:Chloride Channels; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D015742:Propofol