EFFECTS OF SOME CHOLINESTERASE INHIBITORS ON SQUID GIANT AXON - THEIR PERMEABILITY, DETOXICATION AND EFFECTS ON CONDUCTION AND ACETYLCHOLINESTERASE ACTIVITY

The irreversible cholinesterase inhibitors, O,O-diisopropyl S-(2-diisopropyl-aminoethyl) phosphorothioate (Tetriso), O-ethyl Se-(2-diethyiaminoethyl) ethylphosphonoselenoate (Selenophos) and O,O-diethyl S-(2-ethylthioethyl) phosphorothioate (Isosystox), penetrate in their inhibitory forms into the squid giant axon. Tetriso and Selenophos, when applied for 30 min in concentrations as high as 5 × 10-3M, did not block axonal conduction. At that concentration, Isosystox caused either a reversible or an irreversible block of conduction depending on the length of time the nerve was exposed to the inhibitor. After pretreatment of the squid axon with cottonmouth moccasin venom, Selenophos (5 × 10-3M) caused in 25 min a marked and irreversible reduction in the action potential, while Tetriso (5 × 10-3m) caused a rapid and reversible decrease in the action potential. An extremely sensitive, simple radiometric technique for the assay of cholinesterase activity has been developed and is described in detail. Nevertheless, attempts to measure enzyme activity in squid axons exposed to Selenophos or Tetriso were unsuccessful because small amounts of entrapped inhibitor in the tissue were released upon homogenization. Possible explanations for the high concentrations of inhibitors required to affect conduction are discussed. © 1969.