Microscopic Models Of Channel Function

Abstract

The phenomenological models of Chapter 9 are not complete explanations of the voltage-dependent gating, selectivity and permeation processes they are intended to explain. The Hodgkin-Huxley and related models fail to explain microscopic phenomena, such as the depressed Cole-Cole semicircles and the observed fluctuations. In this chapter we examine proposed microscopic models that seek to build a theoretical scaffolding to answer the questions posed in Chapter 1. Noise and admittance studies show that the Na channel is a nonlinear, nonequilibrium system. Neurotoxin studies show that the transition to single-channel sodium conduction is suppressed by a single TTX molecule. We will analyze the conventional view that the channel is a water-filled structural pore before considering alternative models more or less grounded on physical and chemical principles. Since speculation appears to be necessary for a leap to a new paradigm, we will review a number of proposed models, most but not all microscopic.