114 Brain Research, 85 (1975) 114-119 (~) Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands N-Ethylmaleimide-induced conductance changes in the giant neuron of Aplysio ROBERT W. BERRY* ANDDAVID A. WEISBLAT Division of Biology and Division of Chemistry and Chemical Engineering, CaliJbrnia Institute of Technology, Pasadena, Calif. 91109 (U.S.A.) (Accepted November 12th, 1974) Reagents which bind to or oxidize sulthydryl groups have been found to have widespread effects on excitable membranes, suggesting that such groups may have some function in the gating of ionic conductances in such membranes. In certain cases the specificity of action of sulfhydryl reagents has been demonstrated by com- petition with appropriate pharmacological agents. Thus curare inhibits the depolari- zing action of such reagents on frog endplate ~7, and specific odorants can competitively block the effects of sulfhydryl reagents on olfactory receptors 6. Indeed, Karlin and co-workers have used a cholinomimetic SH-binding compound to demonstrate a functionally important SH group in the cholinergic receptor of Electrophorus elec- troplax 9. The action of these reagents is not restricted to chemoreceptors, however, as they can cause conduction block in frog nerve and lobster axon 16, as well as squid axon s . Since loss of excitability preceded any reduction of the resting potential in the latter case, it has been argued that the reagents might be acting directly on electrically- excitable conductance mechanisms s. This idea has received support from experiments of Marquis and Mautner 12 showing that mercurial binding to crustacean nerve is increased by electrical excitation. However, since membrane resistance has never been monitored in these studies, and since SH-reagents can increase K t permeability in erythrocyte membrane ~1, it is important to exclude non-specific permeability in- creases as a cause of conduction failure. We have attempted to investigate this point by determining the effect of N- ethylmaleimide (NEM) on the membrane properties of the giant neuron of the ab- dominal ganglion of Aplysia californica. This cell (R2 of Frazier, et al: 4) was chosen because its large size simplifies conductance measurements, its somatic membrane is electrically excitable ~, and a considerable amount of information is available about its membrane conductances 3,5,13,14. NEM was the sulfhydryl reagent of choice because of its relative specificity for SH groups, the fact that it forms a covalent, and * Present address : Anatomy Department, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, I11, 60611, U.S.A.