Kinetics of etomidate actions on GABAA receptors in the rat spinal dorsal horn neurons

Electrophysiological properties of etomidate (ET)-induced current (IET) at different concentrations and effects of ET at clinically relevant concentrations (1–10 μM) on postsynaptic GABAA receptor function were investigated using whole-cell patch-clamp technique in mechanically dissociated rat spinal dorsal horn neurons. The results showed that ET actions were concentration-dependent: low concentrations (10 μM) of ET potentiated GABA-activated current (IGABA), slowed activation, desensitization and deactivation of GABAA receptors; moderate concentrations (10–1000 μM) of ET directly activated and desensitized GABAA receptors; high concentrations (>1000 μM) of ET produced an inhibitory effect on IET. In addition, ET prolonged the duration of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the mechanically dissociated rat dorsal horn neurons. These results suggest that general anesthetics-induced changes at spinal level could significantly contribute to analgesia and general anesthesia. [Copyright &y& Elsevier]