Ionophore A23187: the effect of proton concentration on complex formation with divalent and monovalent cations and the demonstration of potassium(1+) ion transport in mitochondria mediated by A23187

Abstract

The 2 phase extraction technique was used to study the equilibrium between A23187 (C29H37N3O6), metal cations and H+. Under these conditions the ionophore forms charge neutral isostoichiometric complexes with divalent cations in which both carboxylate groups of the 2:1 A23187:M2+ complexes are deprotonated. In ethanol the methyl ester of A23187 also binds divalent cations, indicating that protonated complexes between A23187 and cations should also exist. With monovalent cations A23187 forms 2 charge-neutral complexes of stoichiometrics and relative stabilities: A2HM > AM. Examination of energy utilization, K+ and H+ movements and light scattering capacity of rat liver mitochondria in the presence of divalent cation chelators, A23187 and valinomycin demonstrates that A23187 can act as a nigericin type K+ ionophore under appropriate conditions. Formation constants for the A2HM complexes with monovalent cations indicate that with appropriate conditions transport of Li+ and Na+ mediated by A23187 would be expected. The binding constant data and associated free energies of complex formation are compared as a function of ionic radius and of cation charge. Lack of conformational mobility in A23187 may be responsible for the high cation size selectivity of this compound. To explain the transport selectivity of A23187 for divalent cations, it is proposed that this ionophore forms a family of 5 complexes, isostoichiometric between cations of different valence but of which only charge-neutral species are permeant to membranes. The charge of a given complex is in turn determined by that of the cation. The concept is consistent with the divalent cation transport specificity of A23187, explains the observed monovalent cation transport and is useful in rationalizing the differences in charge selectivity between A23187 and X-537A (lasalocid).