On the mechanism of halothane anaesthesia.

1. The effects of halothane on the evoked potentials of in vitro preparations of guinea-pig olfactory cortex were studied.2. The evoked potentials recorded from the cortical surface comprised an initial diphasic wave - the lateral olfactory tract (l.o.t.) compound action potential - followed by a negative wave of 1-3 mV amplitude and about 10 msec duration. Superimposed on the negative wave was a number of positive peaks. The negative wave has been identified as an extracellularly recorded, monosynaptic, excitatory post-synaptic potential (e.p.s.p.) and the positive peaks have been shown to reflect the discharge of the cortical cell population in response to the evoked e.p.s.p. and are therefore termed ;population spikes'.3. When halothane (0.4-1.5%) was added to the gas stream that superfused the surface of the preparation the evoked e.p.s.p.s became smaller in amplitude and the size of the population spikes diminished. The l.o.t. compound action potential was unaffected by these levels of halothane. Higher levels of halothane (above 2%) further reduced the amplitude of the evoked e.p.s.p.s, abolished the population spikes, decreased the amplitude of the l.o.t. compound action potential and slowed its time course. The effects of halothane on the evoked potentials were dose-related and were independent (after the first 10 min of treatment) of the duration of the exposure to halothane.4. The decrease in the size of the population spike caused by the exposure to halothane implied that transmission through the cortical relay had been impaired. This was also shown by the decrease in the evoked activity of units in the prepiriform cortex. Of eleven units, eight were depressed by halothane (0.5-1.5%) two were unaffected and one showed a transient increase in the number of spikes generated in response to a l.o.t. volley.5. Halothane (up to 1.5%) had no effect on the threshold of the l.o.t. fibres to electrical stimulation or on that of the post-synaptic cells to synaptic excitation.6. Post-tetanic potentiation and frequency potentiation of the evoked e.p.s.p.s were enhanced in the presence of 1% halothane.7. It is concluded that halothane reduces excitatory synaptic transmission not by an increase in the electrical threshold of the post-synaptic cells to synaptic excitation but by interference with the process of chemical transmission either by reducing the output of transmitter from the pre-synaptic nerve terminal or by reducing the sensitivity of the post-synaptic membrane to the released transmitter substance.