Correlative study of behavior and synaptic events during halothane anesthesia in the lamprey

Behavioral anesthetic effects of halothane were compared with neurophysiological data obtained from monosynaptically coupled, single axon-giant neuron pairs in the isolated central nervous system of the lamprey in vitro. Based on the assumption that the number of halothane molecules at the site of anesthetic action is determined by molar concentration of the bath, depths of anesthesia were characterized in terms of synaptic events. The concentration producing anesthesia in 50% (AC50) and 95% (AC95) of the animals were 0.32 and 0.51 mM, respectively. With these concentrations, the depression of glutamate (GLUT)-mediated synaptic excitation remained less than 50%. Maximum suppression of the excitatory synaptic transmission was observed in the presence of 1.7 mM halothane which would be equivalent to the inhalation of 5.5% of this agent at 37 degrees C. At these concentrations, postsynaptic membranes did not respond to the bath-applied GLUT agonists. The decrease of agonist-induced responses to almost the same extent as excitatory postsynaptic potential (EPSP) amplitudes in the presence of halothane argues against a presynaptic mechanism affecting transmitter release. Persistent voltage-gated Na+ channel function at concentrations less than 2.4 mM is evidence against the involvement of this mechanism at these levels of anesthesia. The present results suggest that with depths between AC50 and AC95, anesthesia is associated with a partial reduction of sensitivity of the postsynaptic membrane to the excitatory amino acid transmitters.