General anesthetics hyperpolarize neurons in the vertebrate central nervous system

The effect of general anesthetics on frog motoneurons and rat hippocampus pyramidal cells was examined with sucrose gap and intracellular recording, respectively. A number of volatile and intravenous anesthetics directly hyperpolarized the motoneurons. The potency of these agents in hyperpolarizing motoneurons was strongly correlated with their anesthetic potency. While the responses to barbiturates and alpha-chloralose were blocked by gamma-aminobutyric acid antagonists and were dependent on the chloride gradient, the responses to all the other anesthetics tested were generated by a separate mechanism. Intracellular recording from hippocampal pyramidal cells suggested that an increase in potassium conductance accounts for these responses. Such a nonsynaptic action would contribute to the decreased neuronal responsiveness observed for these compounds and thus to their anesthetic action.