The action of anaesthetics on stimulus-secretion coupling and synaptic activity.

1. Anaesthetics are known to depress excitatory synaptic transmission and the mechanism of this inhibition has been investigated using bovine adrenal chromaffin cells as an experimental model. 2. These cells are homologous with post-ganglionic sympathetic neurons and have well characterized receptor and secretory mechanisms. They are amenable both to the direct measurement of evoked secretion with its associated ion fluxes, and to electrophysiological investigation using the patch clamp technique. 3. These approaches have been used to study the influence of anaesthetics on pre- and post-synaptic mechanisms involved in stimulus-secretion coupling. 4. A variety of agents inhibited secretion evoked by direct depolarization, and this was shown to be due to a reduction in calcium influx. 5. Direct inhibition of voltage-gated calcium currents was confirmed by whole-cell patch clamp measurements. 6. In addition, anaesthetics powerfully modulated nicotinic receptor mediated events: carbachol-evoked secretion was more sensitive to anaesthetics than that stimulated by high potassium. 7. The mechanism of anaesthetic action on the nAChR was examined in more detail with patch-clamp experiments. 8. These showed that anaesthetics reduced the probability of channels being in the open state, largely as a result of reduction in mean channel open time. 9. The data are discussed in relation to excitatory synaptic transmission.