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

Abstract

Electrophysiological properties of etomidate (ET)-induced current ( I ET) at different concentrations and effects of ET at clinically relevant concentrations (1–10 μM) on postsynaptic GABA A 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 ( I GABA), slowed activation, desensitization and deactivation of GABA A receptors; moderate concentrations (10–1000 μM) of ET directly activated and desensitized GABA A receptors; high concentrations (>1000 μM) of ET produced an inhibitory effect on I ET. 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.