Perspectives on: Ion selectivity

The purpose of the Perspectives in General Physiology is to provide a forum where scientific uncertainties or controversies are discussed in an authoritative, yet open manner. The Perspectives are solicited by the editors— often based on recommendations by members of the editorial advisory board. To frame the issue, two or more experts are invited to present brief points of view on the problem; these are published consecutively in the Journal. One or more experts and the organizer review the contributions, but the comments and opinions expressed in the Perspectives are those of the authors and not necessarily those of the editors or the editorial advisory board. The Perspectives are 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 are published in a single, predetermined issue (usually three months after publication of the Perspective). After the letters to the editor have been published, further responses are limited to full manuscripts. In this issue of the Journal, Youxing Jiang (University of Texas Southwestern Medical Center) together with Amer Alam; Crina M. Nimigean (Weill Cornell Medical College) and Toby W. Allen (University of California at Davis); Benoît Roux (University of Chicago) together with Simon Bernèche, Bernhard Egwolf, Bogdan Lev, Sergei Y. Noskov, Christopher N. Rowley, and Haibo Yu; Dilip Asthagiri (Johns Hopkins University) together with Purushottam D. Dixit; and Susan B. Rempe (Sandia National Laboratory) together with Sameer Varma, David L. Bostick, David Rogers, Lawrence R. Pratt, and Charles L. Brooks III provide different perspectives on the ion selectivity of cation-selective channels and transporters. Current thinking about the mechanisms underlying ion channel selectivity are rooted in concepts dating back to the BC (before crystals) era. Mullins (1959) proposed that the selectivity of excitable membranes arose from the existence of membrane-spanning channels with diameters that were able to accommodate the preferred ion (e.g., Na or K); he further noted that ions preferentially would move through pores that fit them rather well, in order for the pore lining to solvate the permeating ions. Eisenman (1961) developed the