Theorie der Nervenerregung als kooperativer Kationenaustausdi in einem zweidimensionalen Gitter

Abstract

The presently accepted theory of nerve excitation (HODGKIN and HUXLEY, 1952) fails to explain the mechanism of regulation of the state of the axon membrane by the membrane-potential or the cation-activities. We have proposed a physico-chemical mechanism for the regulation of the excitation state based on a model of the axon membrane as a two-dimensional cooperative cation exchanger in contact with the electrolyte reservoirs inside and outside. In the resting state, the lattice units of the cation exchanger bind calcium ions. Upon depolarization or decrease of the calcium activity in the outside medium, the resting state becomes instabil and univalent cations are bound by the lattice units. The ion movements accompanying the cation exchange give rise to the inward excitation current, as observed in a voltage clamp experiment. This cooperative cation-exchange can be considered as a two-dimensional phase transition. Its kinetics have been described by the processes of nucleation and nucleus-growth. The kinetic theory has been applied to measurements of the ionic current in the voltage clamp experiments of COLE and MOORE (1960). The theory describes in good agreement with the experiment the dependence of the ionic current on time and on membrane potential for small depolarizations. Three parameters have to be adjusted in this comparison, two of which have a simple molecular meaning and are given as: a0 = 21 × 21 Å2 =area per lattice unit w = 5.1 Kcal/mol=twice the difference in interaction energy of a lattice unit in the two binding states with the rest of the lattice being in one of the two states. The order of magnitude of these parameters favours the hypothesis of identifying the excitable structural units in the axon membrane with membrane-bound proteins.