Propofol combined with diazepam synergistically potentiates the GABA-activated chloride current in rat sensory neurons

Objective To investigate the effect of propofol combined with diazepam on the gamma-aminobutyric acid (GABA)-activated chloride current (I-GABA) evoked in rat sensory neurons. Methods Whole cell patch clamp recordings were made from cultured rat dorsal root ganglionic neurons. GABA (3 mu mol/L) was applied by pressure ejection. The anesthetics were dissolved in the external solution and given by the "Y-tube" method. Results Co-application of propofol (0.3 - 3 mu mol/L) and diazepam (100 nmol/L) potentiated the I-GABA which was significantly larger than the sum of that potentiated by drug alone. Diazepam (100 nmol/L) shifted the concentration-response curve for the I-GABA potentiation induced by propofol to the left in a parallel fashion. The EC50 value for propofol was decreased by diazepam from 7.6 +/- 1.8 mu mol/l to 3.9 +/- 1.1 mu mol/L (n = 9). Conclusions Our results suggest that propofol combined with diazepam synergistically potentiates the I-GABA Diazepam-induced increase in the apparent binding affinity of propofol for the GABA(A) receptors is likely responsible for a clinical synergistic hypnotic action during co-application with propofol and diazepam.