Mechanism and specificity of lanthanide series cation transport by ionophores A23187, 4-BrA23187, and ionomycin

A23187, 4-BrA23187, and ionomycin transport several lanthanide series trivalent cations at efficiencies similar to Ca²⁺, when compared at cation concentrations of ~10^-5 M, ionophore concentrations of ~10^-6 M, and a pH of 7.00. Selectivity sequences and the range of relative rates are as follows: A23187, Nd³⁺ > La³⁺ > Eu³⁺ > Gd³⁺ > Er³⁺ > Yb³⁺ > Lu³⁺ (~34-fold); 4-BrA23187, Nd³⁺ > Eu³⁺ > Gd³⁺ > La³⁺ > Er³⁺ > Yb³⁺ > Lu³⁺ (~34-fold); ionomycin, La³⁺ > Yb³⁺ > Nd³⁺ > bu³⁺ > Er³⁺ > Eu³⁺ > Gd³⁺ (~4-fold). At concentrations between 9 and 250 μM, La³⁺ is transported by an electroneutral mechanism, predominately through mixed complexes of the type (ionophore)₂La·OH (A23187 and 4-BrA23187) or (ionophore)La·OH (ionomycin), when no membrane potential is present. For all three ionophores, an induced potential of ~160 mV accelerates transport by ~50-100%. However, measured values of H⁺/La³⁺ exchange indicate that only 4-BrA23187 displays a significant electrogenic activity under these conditions. At a La³⁺ concentration of 17 mM, transport by all three ionophores is electroneutral and apparently occurs through complexes of type (ionophore)₃La (A23187 and 4-BrA23187) or (ionophore)La·OH (ionomycin). Analysis of these patterns in a context of comproportionation equilibria involving the transporting species and free La³⁺ indicates that the species containing three ionophore molecules are formed on the membrane when aqueous phase solution conditions would strongly favor a 1:1 complex, based upon previous studies in solution. The implications of this and other findings are discussed.