Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: I. Tetranactin and the methylation of nonactin-type carriers.

The manner in which molecular structure of the carrier and the lipid composition of the membrane modulate the membrane selectivity among monovalent cations has been investigated for nonactin, trinactin, and tetranactin, which differ only in their degrees of methylation, and for membranes made of two lipids, phosphatidyl ethanolamine and glyceryl dioleate, in which "equilibrium" and "kinetic" aspects of permeation, respectively, are emphasized. Bilayer permeability ratios for Li, Na, K, Rb, Cs, Tl,and NH4 have been characterized and resolved into "equilibrium" and "kinetic" components using a model for carrier-mediated membrane transport which includes both a trapezoid energy barrier for translocation of the complex across the membrane interior and a potential-dependence of the loading and unloading of ions at the membrane-solution interfaces. The bilayer permeability properties due to tetranactin have been characterized in each of these lipids and found not only to be regular but to be systematically related to those of the less methylated homologues, trinactin and nonactin. This analysis has led to the following conclusions: (1) The change in lipid composition alters the relative contributions of "kinetic" vs. "equilibrium" components to the observed carrier-mediated selectivity. (2) Increased methylation of the carrier increases the contribution of the "kinetic" component to the selectivity relative to that of the "equilibrium" component and additionally alters the "equilibrium component sufficiently that an inversion of Cs--Na selectivity occurs between trinactin and tetranactin. (3) For all ions and carriers examined, the "reaction plane" for ion-carrier complexation and the width for the "diffusion barrier can be represented by the same two parameters, independent of the ion or carrier, so that in all cases the complexation reaction senses 10% of the applied potential and the plateau of the "diffusion barrier" extends across 70% of the membrane interior.