Chemical basis of ion transport specificity in biological membranes

Abstract

This review addresses the issues of the chemical and physical processes whereby inorganic anions and cations are selectively retained by or passed through cell membranes. The channel and carrier mechanisms of membranes permeation are treated by means of model systems. The models are: the planar lipid bilayer for the cell membrane, Gramicidin for the channel mechanism, and Valinomycin for the carrier mechanism.

With respect to the channel mechanism, the phenomenology of channel transport is noted; the molecular structure of the Gramicidin channel is briefly reviewed; the cation binding sites are located within the channel; using Eyring rate theory a free energy profile for ion transit through the channel is developed based on the location of the binding site and the determination of binding and rate constants by physical methods which are independent of the transport mechanism, and it is demonstrated that both binding site location and rate constants must be independently determined in order to achieve the unique description of ionic mechanism. It is shown that inorganic anion vs cation selectivity is the result of the chemical structure of polypeptides combined with conformational energetics of the channel; it is shown that monovalent vs multivalent cation selectivity is the result of the proximity of membrane lipid to the channel proper and properties are proposed for a divalent cation channel; and it is argued that selectivity among monovalent cations is enhanced by the conformation energetics of the channel. Furthermore, a formalism is given which leads to a means of evaluating thermodynamics relative to selectivity among monovalent cations.

With respect to the carrier mechanism, the phenomenology of the carrier transport of ions is discussed in terms of the criteria and kinetic scheme for the carrier mechanism; the molecular structure of the Valinomycin-potassium ion complex is considered in terms of the polar core wherein the ion resides and comparison is made to the Enniatin B complexation of ions; it is seen again that anion vs cation selectivity is the result of chemical structure and conformation; lipid proximity and polar component of the polar core are discussed relative to monovalent vs multivalent cation selectivity and the dramatic monovalent cation selectivity of Valinomycin is demonstrated to be the result of the conformational energetics of forming polar cores of sizes suitable for different sized monovalent cations.

It should be apparent that the principles of selective ion transport are independent of the specific models being treated here and that many of these principles are at variance with what were traditional views on the basis of selective membrane permeation by inorganic ions. Thus, the concept of selectivity among monovalent cations being based on values of hydrated radii is replaced by the demonstration that greater selectivity comes with increased dehydration. The perspective that hydration is the best way to lower ion self energy in order to pass through a protein component in a cell membrane is replaced by demonstration that peptide and ester carbonyls are far better solvators than water and that what is critical is the conformational energetics required to achieve adequate coordination. Furthermore, the earlier prevalent view that the repulsive image force due to the presence of the lipid layer would cause the rate limiting barrier to be in the middle of the membrane is shown to be entirely incorrect for monovalent cations but relevant indeed to multivalent cations. It should also be appreciated that there are other physiocochemical data available from these model systems such as the repulsion between ions at a known distance and separated by a string of water molecules and such as the energetics of lipid membrane deformation. Such information while relevant to the mechanisms of selective permeation of cell membranes has a more general and widespread application.