Electrical activity in electric tissue I. The difference between tertiary and quaternary nitrogen compounds in relation to their chemical and electrical activities

Abstract

1. 1. The resting and action potentials of isolated electroplax of Electrophourus electricus have been recorded by means of intracellular electrodes, and their changes by compounds reacting specifically with the acetylcholine system have been studied. 2. 2. A method has been developed which permits the assay of a major portion (about two-thirds_) of acetylcholinesterase activity in intact electroplaques. The procedure is based upon the use of ethyl chloroacetate as the substrate. 3. 3. The combination of these two methods made possible a correlation between the effect on the electrical potentials and that on the enzyme activity. 4. 4. The compounds tested can be divided into two groups: 4.1. i. Those which do not significantly affect the enzyme. This group comprises carbamylcholine, decamethonium and procaine. Acetylcholine, dimethylaminoethyl acetate and d-tubocurarine, not tested here in relation to esterase inhibition, are regarded as belonging to this group. 4.2. ii. Those which depress the assayable acethylcholinesterase activity to alos level at the time block of propagation of the action potential along the cell occurs; eserine, DFP, prostigmine and its tertiary analogue belong to this group. 4.3. 5. All the quaternary compounds tested except d-tubocurarine block the spike and simultaneously depolarize the electroplaque membrane. All the tertiary compounds, except dimethylaminoethyl acetate, block the propagation of the spike without depolarization. 4.4. 6. DFP blocks the conduction of the spike without simultaneous depolarization. 4.5. 7. The depolarization caused by carbomylcholine is antagonized by procaine, eserine, d-tubocurarine and the tertiary prostigmine analogue. 4.6. 8. It is concluded that the compounds which do not depolarize, block propagation of the action potential by competition with acetylcholine for the same receptor. A similar mechanism underlies their antagonism to carbamylcholine. These result suggest that the combination of a substance with the acetylcholine receptor does not necessarily cause depolarization. The latter effect is apparently determined by a special change of the receptor attending the binding of a specif chemical structure, in which one important characteristic seems to be the presence of a methylated quaternary nitrogen group. 4.7. 9. The results are discussed in connection with previous observations with the enzyme proteins of the system in solution.