Effect of Curare on Conduction in Myelinated, Isolated Nerve Fibres of the Frog

Abstract

THE inhibitory effect of curare on the transmission of nerve impulses across myoneural junctions is generally attributed to its binding with the specific acetylcholine receptors in the motor end-plate membranes in competition with the acetylcholine, thereby preventing the ester from exerting its depolarizing action. Since the work of Claude Bernard, it has been known that curare acts specifically on the motor end-plates without any effect on axonal conduction. The failure of externally applied acetylcholine to affect conduction of nerve fibres was explained by Nachmansohn¹ as being due to permeability barriers surrounding the axon which are impermeable to lipid-insoluble compounds, such as methylated quaternary nitrogen derivatives, and cannot reach, therefore, the interior of the axon. These permeability barriers also explain the absence of any action of curare on axonal conduction: if monoquaternary ammonium salts are unable to penetrate these barriers, it is certainly to be expected that diquaternary salts will not enter. This does not indicate that the acetylcholine receptor upon which curare is supposed to act at the myoneural junction is not present and functional in the axon, only that it cannot be reached. If this viewpoint is correct, then diquaternary compounds which have two cationic nitrogens at the proper distance but are in addition soluble in lipid, such as stilbamidine, should have curare-like action. Block of conduction by stilbamidine was obtained by Bergmann, Wilson and Nachmansohn² on the axon, and by Schoffeniels and Nachmansohn³ on the conducting membrane of the electroplax of Electrophorus electricus.