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. 2018 Jul 9;8:10341. doi: 10.1038/s41598-018-28754-7

Figure 5.

Figure 5

Activation and modulation of concatemeric α1β2γ2L GABAA receptors. (A) Direct activation of the receptor by GABA, propofol (PRO), or alfaxalone (ALF). The ordinate shows the estimated open probability (Po). The curves for GABA and propofol were generated by fitting Equation (1) to experimental data. Direct activation by alfaxalone produced very small currents (<100 nA at 30 μM). The predicted activation curve for alfaxalone was generated using KALF and cALF values determined in (B). (B) Potentiation of GABA-activated receptors by propofol, alfaxalone, or diazepam (DZP). The solid curves were generated by fitting Equation (1) to the data. L was held at (1 − Po,2 μM GABA)/Po,2 μM GABA. The dashed line shows the predicted propofol-potentiation curve using KPRO and cPRO values from (A). (C) Activation by GABA in the presence of 1 μM diazepam, 1 μM alfaxalone or the combination of diazepam + alfaxalone. The curves for single modulators were generated by fitting Equation (1) to the data. L was held at at (1 − Po,1 μM ALF)/Po,1 μM ALF or at (1 − Po,1 μM DZP)/Po,1 μM DZP . The open probability for receptors activated by 1 μM alfaxalone or 1 μM diazepam was calculated from the KALF and cALF, or KDZP and cDZP values estimated in (B). The simulated curve for the combination of diazepam + alfaxalone was calculated using Equation (1) and the KGABA and cGABA values from (A), and KALF, cALF, KDZP and cDZP values from (B). (D) Activation by GABA in the presence of 10 μM propofol, 1 μM alfaxalone or the combination of propofol + alfaxalone. The curve for propofol (green dashed line) is based on data from a previous report45. The data for alfaxalone are reproduced from panel C. The simulated curve for the combination of propofol + alfaxalone was calculated using Equation (1) and the KGABA, cGABA, KPRO and cPRO values from (A), and KALF and cALF values from (B). In (C) and (D), the black dotted lines show the GABA concentration-response relationship in the absence of modulators (from A). In all panels the data points show mean ± S.D. from at least five cells.