The actions of propofol on γ-aminobutyric acid-A and glycine receptors in acutely dissociated spinal dorsal horn neurons of the rat

The spinal cord plays an important role in modulating anesthetic -induced suppression of nociceptive transmission. To gain some insight into the anesthetic mechanisms of propofol at the spinal level, we investigated the direct action of propofol and its modulation on the γ-aminobutyric acid-A receptor (GABA_AR) and the glycine receptor (GlyR) in acutely dissociated rat spinal dorsal horn neurons by using whole-cell patch-clamp electrophysiology. Propofol induced Cl^- currents (I_Cl), which were sensitive to bicuculline and, to a lesser extent, to strychnine. The activation, desensitization, and deactivation of propofol-induced I_Cl were slower than those of GABA- and glycine-induced I_Cl. In addition, this study revealed similar modulatory actions of propofol on GABA_AR and GlyR. Propofol potentiated both GABA- and glycine-induced I_Cl at small concentrations and inhibited both GABA- and glycine-induced I_Cl at large concentrations. The potentiation of propofol on I_Cl was caused by slowing current desensitization and deactivation, whereas the inhibition actions might be involved in the cross-desensitization between GABA- and propofol-induced I_Cl and the cross-inhibition between the GABA_AR and GlyR. The results suggest that propofol facilitation of GABA_AR and GlyR at the spinal level could contribute significantly to general anesthetic-induced analgesia and anesthesia.