Reversible Block of Axonal Conduction by Curare after Treatment with Cobra Venom and a Detergent

Abstract

THE recent experiments of Abbott, Hill and Howarth¹ have revealed that the remarkably high initial heat produced in nerve fibres coincides roughly with electrical activity. This finding re-emphasizes the necessity of explaining electrical activity on a chemical basis. Nachmansohn's theory² attributes the change of conductance which initiates the ion movements to the reaction of acetylcholine with a receptor protein. One of the main objections to this theory is the lack of effect of acetylcholine and curare on axons in contrast to their powerful action at junctions. This failure was attributed to the existence of structural barriers for lipid-insoluble quaternary ammonium compounds. Evidence supporting this contention was obtained in experiments on squid giant axons: acetylcholine, labelled with nitrogen-15, and prostigmine failed to penetrate into the axoplasm whereas lipid-soluble tertiary compounds did so readily^3,4. However, at the nodes of Ranvier, where these barriers are relatively small, curare can rapidly and reversibly block conduction, as shown in recent work by Dettbarn⁵. Walsh and Deal⁶ succeeded in partially breaking down these barriers in frog sciatic nerve by treatment with the cationic detergent cetyltrimethyl-ammonium bromide, after which curare and other quaternary ammonium compounds, ordinarily inert on the intact axon, caused reversible block of conduction.