Nerve excitability--toward an integrating concept.

Although numerous experimental data have been accumulated in the various fields of research on bioelectricity, the mechanism of nerve excitability is still an unsolved problem. Many mechanistic interpretations of nerve behavior cover only a part of the facts, are thus selective and unsatisfactory. An attempt at an integral interpretation of basic data well-established by electrophysiological, biochemical, and biophysical investigations was inspired by the late Aharon Katchalsky and a first attempt had been made previously (Neumann et al., 1973). The present account is a further step toward a quantitative physiochemical theory of bioelectricity. We have further explored the previously introduced notion of a basic excitation unit in excitable membranes. This notion is of fundamental importance for modeling details of sub- and suprathreshold responses, such as threshold behavior and strength-duration curves, in terms of kinetic parameters for specific membrane processes. Our integral model of excitability is based on the original chemical hypothesis for the control of bioelectricity (Nachmansohn, 1959, 1971b). This specific approach includes some frequently ignored experimental facts on acetylcholine-processing proteins in excitable membranes. According to the integral model, acetylcholine ions are continuously processed through the basic excitation units within excitable membranes: axonal, presynaptic, and postsynaptic parts. Excitability, i.e., the generation and propagation of nerve impulses, is due to a cooperative increase in the rate of AcCh translocation through the cholinergic control system.