Quarterly Reviews of Biophysics 25, 4 (1992), pp. 459-475 459 Printed in Great Britain Kinetic analysis of lipid soluble ions and carriers S. B. HLADKY Department of Pharmacology, University of Cambridge, Tennis Court Rd., Cambridge CB2 iQJ 1. INTRODUCTION 459 2. LIPID SOLUBLE IONS 459 3. KINETICS OF NEUTRAL CARRIERS OF CATIONS 465 4. REFERENCES 473 1. INTRODUCTION The advent of methods for forming and studying lipid bilayer membranes (Mueller et al. 1962; Hanai et al. 1964) opened the way for some fifteen years of intensive and productive study of the properties of lipid soluble ions and ion carriers. I expect that none will dissent from the view that Peter Lauger and his associates, including R. Benz and G. Stark, did more than any other research group to advance the study of the mechanism of the charge transfer. Between 1970 and 1981 they published more than 25 substantial contributions. Thus it is appropriate that this memorial issue should contain a short review of this subject. As I have the highest regard for their work I was very pleased to be asked to write such a chapter. There is little point in providing another general survey because Lauger's group published reviews at the end of this period (Benz et al. 1980; Lauger et al. 1981) and I also reviewed the field at length (Hladky, 1979a). Instead I would like to consider the three cornerstone papers of 1971, some of the difficulties that arose from those papers, how they were overcome, and three aspects of the description that are still incomplete. 2. LIPID SOLUBLE IONS As indicated in Fig. 1 any stationary membrane has on either side a region in which transport perpendicular to the membrane occurs primarily by diffusion rather than by convection. Though this region is actually neither unstirred nor a layer, it is called the unstirred layer. Prior to the publication by Ketterer et al. (1971) others had investigated the fluxes of lipid soluble ions across bilayers but the work had concentrated on the steady-state currents and the slow time