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.