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 muM GABA (gamma-aminobutyric acid) or GABA alone. The propofol-activated currents were chloride-selective, showed outward-rectification and were enhanced by 1 muM diazepam. The maximum propofol-activated channel conductance increased with propofol concentration from less than 15 pS (10 muM) to about 60 pS (500 muM) but decreased to 40 pS in 1 mM propofol. Fitting the data from 10 to 500 muM propofol with a Hill-type equation gave a maximum conductance of 64 pS, an EC50 value of 32 muM and a Hill coefficient of 1.1. Addition of 0.5 muM GABA shifted the propofol EC50 value to 10 muM 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 muM diazepam was added together with a saturating propofol concentration and GABA. The results are compared to effects other drugs have on GABA(A) channels conductance. (C) 2003 Elsevier Science B.V All rights reserved.