ANTICHOLINESTERASE ACTIVITY OF ACID AS A BIOLOGICAL INSTRUMENT OF NERVOUS INTEGRATION

Abstract

The primary premise underlying the humoro-electrotonic theory of mediation is that acetylcholine is highly electrogenic at its site of liberation. Synaptic potentials created by the liberation of acetylcholine in synaptic bombardment of a nerve cell body and its dendrites add their effects one to another and generate a common electrotonic current which flows from the dendrites to the axon hillock in the internal circuit and out through the axon hillock membrane back to the dendrites in the external circuit. The membrane of the axon hillock is detonated at the site of emergence of the electrotonic current at a rhythm proportional to the intensity of the current. The intensity of the current varies with the area of synaptic activity and the sum total of free electrogenic acetylcholine. By virtue of the anticholinesterase activity of acid, physiologic changes of cH cause parallel changes in the sum total of free acetylcholine driving the nerve cells. Synaptic bombardment remaining constant, the acetylcholine pools attain higher or lower levels of conc. with in-creasing and decreasing cH, thus generating stronger or weaker electrotonic currents of proportional motivating power. The greater summation and after-dischrage produced by faradic stimulation of Hering''s nerve during hypercapnia and the lesser effects during hypocapnia uphold this view. Observations collected from the older literature and from the recent expts. of Eccles add strong support. The conclusion therefore seems warranted that CO2 does not stimulate the respiratory center, but indirectly determines the effectiveness of prevailing synaptic bombardment. It is proposed that acid-humoral mediation is the basic mech-anism about which the details of the control of breathing were built. As judged by evolutionary evidence acid-humoral is a primitive mechanism of long standing whose development served to meet the needs of a continuing supply of energy. The occurrence of acid-humoral mediation throughout the C.N.S. and peripheral cholinergic systems in higher forms evidences a general retention of a mechanism originally designed for the primary purpose of providing energy. Survival of the acid-humoral mechanism is thought to impress certain basic characteristics of nervous integration throughout the C.N.S. Of these characteristics, electrotonic mediation is regarded as the most significant. Summation of stimuli, after-discharge, intimately connected half-centers, dual excitatory afferents, reciprocal inhibition and precedence of stimulation would seem to be a natural outgrowth of humoro-electrotonic mediation.