Volatile anaesthetics: cellular mechanisms of action

The mechanisms by which volatile anaesthetics act in the central nervous system are reviewed. The main cellular targets are excitatory synapses and the cell membrane of the neuronal cell body/dendrite, although there also appears to be a significant effect on thin unmyelinated fibres. Experiments quantifying these effects have shown that 1 MAC isoflurane reduces the activity in afferent fibres by 18%, excitatory synapses by 27% and postsynaptic neurones by 24%. Two important effects observed when recording from individual neurones are hyperpolarization of the cell membrane by an enhanced potassium conductance and increased threshold for initiation of action potentials. Excitatory synaptic transmission is most probably reduced due to a decreased release of transmitter from presynaptic terminals. Antagonistic and biphasic effects are often seen, for instance depression of both inhibitory and excitatory transmission and depolarization-hyperpolarization of the postsynaptic membrane.