General anaesthetics and field currents in unclamped, unmyelinated axons of rat olfactory cortex.

1. The effects of seven general anaesthetics and one local anaesthetic having a wide range of physical and chemical properties were studied on nerve terminal Na- and K-mediated currents in slices of olfactory cortex. These currents were measured from the groups of fine unmyelinated axons traversing the surface of the olfactory cortex and which give off synapses en passant. The amplitude of the K-current was visualized by depolarizing the axons via an electrode polarization. 2. The anaesthetics tested were ketamine (0.1-2 mM), pentobarbitone (0.1-5 mM), urethane (5-200 mM), halothane (0.5-5 mM), ether (10-200 mM), alphaxalone (0.001-0.05 mM), diisopropylphenol (0.05-0.5 mM) and lignocaine (0.01-0.5 mM). All had depressant effects on the axonal Na-current (at the higher concentrations tested) and on the K-current (at slightly lower concentrations). The apparent lower potency on the Na-current was considered to be due to a masking of effect as a consequence of the reduction in the K-mediated membrane rectification rather than any real difference in the susceptibilities of the Na and K-currents. 3. Some of the depressant effect of pentobarbitone and alphaxalone was gamma-aminobutyric acid (GABA)-mediated as indicated by the reduced potency in the presence of bicuculline. The actions of ketamine and halothane were unaffected by bicuculline. 4. For some anaesthetics these axonal depressant effects might contribute to general anaesthesia, while for other substances the relatively high concentrations necessary would suggest that this mode of action does not produce effective anaesthesia in vivo.