Anaesthetics, Convulsants, And The Squid Axon Membrane
The use of the squid axon as a model system for the study of anaesthetic mechanisms is described. Effects are divided into actions on the voltage-gated Na and K channels and actions on a voltage-independent K conductance system of the nerve membrane. Inhibition of axonal function by anaesthetics arises largely from effects on the Na channel. The precise nature of these effects varies with the physico-chemical properties of the anaesthetic considered, but certain general principles emerge. Small non-polar anaesthetics tend to increase the resting fraction of Na channels in the inactivated state. The actions of certain fluorinated anaesthetics and convulsants on the squid axon are described in the context of the close relationship between anaesthetic and convulsant actions. At low concentrations these molecules all appear capable of increasing axonal excitability and reducing the threshold for action potential generation. This action is related to the inhibition of a resting K permeability system in the axon membrane. The anaesthetics and convulsants can be distinguished in this axonal model on the basis of their relative potencies for inhibition of resting K permeability and Na channels. Convulsants appear to be characterized by an ability to inhibit the resting K permeability, but are inactive, even at high concentrations, on the Na channel. It is suggested that these properties may parallel the wider biological actions of anaesthetics and convulsants including actions on the central nervous system.
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