Kinetics of etomidate actions on GABA(A) receptors in the rat spinal dorsal horn neurons.
Electrophysiological properties of etomidate (ET)-induced current (I(ET)) at different concentrations and effects of ET at clinically relevant concentrations (1-10 microM) 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 microM) of ET potentiated GABA-activated current (I(GABA)), slowed activation, desensitization and deactivation of GABA(A) receptors; moderate concentrations (10-1,000 microM) of ET directly activated and desensitized GABA(A) receptors; high concentrations (>1,000 microM) 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.
Zhang
Zhen-Xiong
ZX
Laboratory of Receptor Pharmacology, Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, P.O. Box 4, Hefei 230027, China.
Lü
Hui
H
Dong
Xian-Ping
XP
Liu
Jin
J
Xu
Tian-Le
TL
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D005045:Etomidate / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005045:Etomidate