Perspectives on Ion Permeation

The purpose of the Perspectives in General Physiology is to provide a forum where scientific uncertainties or controversies can be discussed in an authoritative, yet open manner. The Perspectives are solicited by the editors—often based on recommendations by the advisory editors or members of the editorial board, who may be asked to coordinate the process. To frame the issue, two or more experts will be invited to present a brief point of view on the problem, which will be published consecutively in The Journal. The comments and opinions expressed in the Perspectives are those of the authors and not necessarily those of the Editors or the Editorial Board. The Perspectives will be accompanied by a few editorial paragraphs that introduce the problem—and invite the submission of comments, in the form of letters-to-the-editor, which will be published in a single, predetermined issue (usually four months after publication of the Perspectives). provide different insights into ion permeation through membrane-spanning channels. Following the lead of Julius Bernstein, who almost 100 yr ago used electrodiffusion theory to describe the resting membrane potential of muscle and nerve, ion movement across biological membranes has traditionally been described using the Nernst-Planck electrodiffusion equations. Beginning in the mid-1950's, however, descriptions of ion movement through membranes moved beyond the conventional implementation of the Nernst-Planck analysis. First, it was found that K ϩ movement through voltage-dependent potassium channels could not be described by the Nernst-Planck electrodiffusion equations, as the flux-ratio exponent describing the K ϩ tracer flux was much larger than the expected value of 1. This led to the notion of single-file flux (Hodgkin and Keynes. 1955. Second, ion–ion interactions within the membrane were introduced explicitly into the Nernst-Planck flux equations via the Poisson equation (Bruner, L.J. 1965. Biophys. J. 5:867–886). Third, it became apparent that ion channels were not simple aqueous pores: they could concentrate ions and exhibit saturation behavior. The latter property was not readily accounted for by the Nernst-Planck equations, which led to the development of rate-theory An attraction of rate-theory models was that they not only provided a convenient way to incorporate flux saturation , they also could account for single-file flux coupling. Moreover, they might provide a way to relate the kinetics of ion movement to the underlying energetics of ion solvation by the channel (provided that the rate constant [ r ] for the transition from an energy well across an adjacent energy …