General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons.
The effects of halothane, isoflurane, and enflurane on ionic currents induced by bath application of gamma-amino-butyric acid (GABA) were studied with the rat dorsal root ganglion neurons maintained in primary culture. The whole-cell patch clamp technique was used to record the current. In normal neurons before exposure to anesthetics, GABA at low concentrations (1-3 x 10(-6) M) induced a small sustained inward current. At higher concentrations (3 x 10(-5) M-1 x 10(-3) M), GABA induced a large inward current, which decayed to a steady-state level (desensitization). Halothane (0.86 mM), isoflurane (0.96 mM), and enflurane (1.89 mM), each equivalent to the respective 2 minimum alveolar concentration (MAC) units, augmented the sustained current evoked by 3 x 10(-6) M GABA to 330-350% of control and the peak current evoked by 3 x 10(-5) M of GABA to 136-145% of control. The decay phase of the current was accelerated by the anesthetics, the time for the current to decline to 70% of the peak being reduced to 23-39% of control. In contrast, the densitized steady-state current evoked by high concentrations of GABA was decreased by anesthetics. In conclusion, general anesthetics exert a dual effect on the GABA receptor channel complex: to potentiate the nondesensitized (both peak and sustained) current and to suppress the desensitized steady-state current. The potentiation of the GABA receptor channel response may be a primary action of anesthetics leading to surgical anesthesia.
Nakahiro
M
M
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Yeh
J Z
JZ
Brunner
E
E
Narahashi
T
T
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D004737:Enflurane / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000777:Anesthetics; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane