EFFECTS OF INHIBITORS OF CHOLINE ESTERASE ON THE NERVE ACTION POTENTIAL

Abstract

Eserine reversibly alters or abolishes the action potentials of giant axon and ordinary peripheral nerve of the squid, Loligo pealii. Before abolition the single fiber action potential is prolonged, slowed in conduction and reduced in amplitude. The observations are consistent with the concept that acetylcholine (ACh), released, acting and removed intracellularly, is involved in the depolarization of the surface membrane not only at nerve endings but along the nerve fiber as well. Prostigmine has no such effect although an equally strong choline esterase inhibitor in vitro. Eserine is a tertiary amine which, in its undissociated form, can be expected to pass through the lipid membrane. Prostigmine, like ACh, is a quaternary ammonium compound, and would therefore not be expected to penetrate the lipid membrane. These expectations were verified by analysis of the extruded axoplasm after soaking nerves in these 2 drug solns. Strychnine, another chemical with a high affinity for choline esterase, also alters and abolishes the action potential, reversibly. Cocaine and procaine act similarly but in concs. such as to make it improbable that the effect is due to inhibition of choline esterase. The expts. offer an explanation of the lack of effect of ACh applied externally to the axon while it exerts an effect at nerve endings: in the latter case, the absence of a myelin sheath (present on all peripheral nerve fibers so far examined, even "unmyeli-nated") makes penetration possible. The expts. are considered to strengthen the concept that the physico-chemical mechanism of conduction along axon does not differ fundamentally from transmission across synapse.