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  • Title: Potentiation, activation and blockade of GABAA receptors by etomidate in the rat sacral dorsal commissural neurons.
    Author: Hong Z, Wang DS.
    Journal: Neuroscience; 2005; 132(4):1045-53. PubMed ID: 15857709.
    Abstract:
    Etomidate (ET), an imidazole general anesthetic, has been medically widely used. Recent evidence suggests that the inhibitory neurotransmitter GABA receptor may be one of the important molecular target(s) of general anesthetics. Up to date, little attention has been directed toward the sacral dorsal commissural nucleus (SDCN), which serves as a relay of sensory information from the pelvic viscera in the spinal cord. Therefore, the effect of ET on GABA(A) receptor function in neurons acutely dissociated from the SDCN was investigated using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. At a holding potential of -40 mV, ET (above 10 microM) induced an inward ET-activated current (I(ET)) with the EC(50) value of 33 +/- 3 microM, which was reversibly blocked by bicuculline and picrotoxin. The reversal potential of I(ET) was close to the Cl(-) equilibrium potential. ET also displayed a biphasic modulatory effect on GABA responses. At lower concentrations (0.1-100 microM), ET reversibly potentiated GABA (1 microM)-activated Cl(-) currents in a bell-shaped manner, with the maximal facilitative effect at 10 microM, whereas at concentrations >100 microM, the peak of the ET-induced current was suppressed in the absence or presence of GABA (1 microM). These results suggest that in SDCN, in addition to the potentiation of GABA(A) receptor-mediated responses at low concentrations and the direct activation of GABA(A) receptors at moderate concentrations as expected, ET produced a fast blocking action at high concentrations. The general anesthetic-induced effects in SDCN, at least the potentiation of GABA responses, may significantly contribute to anesthesia of pelvic viscera during the general anesthesia.
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