Effects of propofol or midazolam combined with fentanyl on GABA_A receptor in hippocampal pyramidal neurons of rats

Objective To observe the effects of propofol or midazolam combined with fentanyl on GABA_A receptor in acutely dissociated hippocampal pyramidal neurons of neonatal rats, so as to reveal the possible mechanism of the combined anesthesia. Methods Whole-cell patch-clamp technique was used to record the GABA_A receptor-induced currents (I_GABA) in four groups(n=5 of each), ie, propofol(groupⅠ), propofol combined with fentanyl(groupⅡ), midazolam (groupⅢ) and midazolam combined with fentanyl(groupⅣ). Results 0.3-30.0 μmol/L propofol (groupⅠ,Ⅱ) and 0.03-100.0 μmol/L midazolam (groupⅢ, Ⅳ) facilitated I_GABA with the greatest enhancement at 3.0 μmol/L of each (P0.05). Following 0.01 μmol/L fentanyl pretreatment for 10 minutes, the facilitation of I_GABA by 3.0 μmol/L propofol increased significantly [(127.2±11.2)% (groupⅠ) vs (212.5±14.9)% (groupⅡ), P0.05, n=5], whereas the effects of midazolam were not changed by fentanyl pretreatment [(158.2±34.0)% (groupⅢ) vs (116.3±46.0)% (groupⅣ), P0.05, n=5]. Conclusion Fentanyl can enhance the effects of propofol on GABA_A receptor, but not influence those of midazolam. Propofol or midazolam combined with fentanyl may prevent the neuroexcitatory effects of fentanyl, supporting their use in combination for clinical anesthesia.