Studies Ox Cholinesterase*

Recent investigations have provided evidence that the release and removal of acetylcholinc is an intracellular process directly connected with the nerve action potential. The experiments suggest that the ester renders the neuronal surface permeable to all ions and thereby depolarizes the membrane (l-4). This concept is based mainly on studies of the enzyme cholinesterase. Three essential features are (a) the high concentration of the enzyme in nervous tissue, a concentration sufficiently high to make possible a rate of acetylcholine metabolism which parallels that of electric changes; (b) the localization of the enzyme at the neuronal surface where the bioelectrical phenomena occur; and (c) the parallelism between the enzyme activity and the voltage of the nerve action potential. In these investigations it was assumed that the enzyme studied is a specific enzyme and that the substrate metabolized is acetylcholine (ACh). Only if this is the case is it justifiable to draw conclusions from the concentration of an enzyme as to the possible rate of the metabolism of the substrate or its function in the cell. It appears necessary, therefore, to ascertain the properties of cholinesterase and, in order to test the new concept of the r&e of ACh in the mechanism of nervous action, to establish the identity of the enzyme in the variety of tissues that were used. The results obtained are to be described in t.his paper and others to follow.