Reflections on Selectivity

Abstract

I entered the field of biophysics well after the conclusion of what B. Hille (13) has aptly called the heroic era, when “the membraneionic theory of excitation was transformed from untested hypothesis to experimental fact.” By that time it was clear that the basic outlines of the Hodgkin and Huxley formulation were there to stay and that anyone wishing to do useful work in the area must accept that. In fact K. S. Cole told me that he thought it would be twenty-five years before enough new information was available to require a new formulation. Given this framework, the research questions worth pursuing dealt with the physical mechanisms underlying the phenomena that A. L. Hodgkin and A. F. Huxley had described with such power. There were three major questions. 1) How do ions pass through membranes? 2) How does the membrane select among monovalent cations? 3) How does the membrane change its dominant permeability in a fraction of a millisecond? All of the questions are closely related or, as in the case of the first two, virtually inseparable. Here I deal only with the question of selectivity. The scope of this chapter is mainly limited to a discussion of the ideas of Lorin Mullins and George Eisenman. Their theories are quite different in character, with Mullins emphasizing the importance of steric considerations, whereas Eisenman virtually eliminates steric factors in his theory and deals only with electrostatics and hydration energies. Even with this limitation of scope, I found that as the chapter progressed I had much to learn.