Towards a molecular theory of the nerve membrane: Inactivation

Abstract

The inactivation properties of a model of the nerve membrane are examined. The inactivation kinetics are closely first order and may be characterized by Hodgkin-Huxley (H-H) parameters h ∞ and τ h which depend on potential in agreement with experiments. Some differences from the H-H equations are identified. The forms predicted for τ h variation with hyper-polarization and change of external [K +] agree with available data. While the inactivation time delay predicted by the model is too small to be detected experimentally, there are grounds for expecting that it may be larger in other tissues, as observed in Myxicola giant axons. The variation of the delay with test potential is predicted to be exponential. Although the model is coupled in the sense defined by Hoyt, it gives rise to an inactivation shift of negligible magnitude. However, introducing a simple variability in one physical parameter leads to the observed form of both the peak transient current voltage relation and the inactivation shift. Inactivation shift thus does not unambiguously indicate coupling; that it results from parametric heterogeneity may be a better hypothesis, and is readily testable. The inactivation shift dependence on current ratio, from experimental data, can be used to correct for the effects of parametric heterogeneity and obtain the value of a previously predicted fundamental parameter of excitable membranes. It is suggested that the effects of parametric heterogeneity must be considered in interpreting experiments and designing models for excitable systems.