Effects of variation of ion and methylation of carrier on the rate constants of macrotetralide-mediated ion transport in lipid bilayers.

The effects of methylation on the rate constants of carrier-mediated ion transport have been studied on monooleindecane bilayers with K+, Rb+, NH4+, and Tl+ ions, using the series of homologue carriers, nonactin, monactin, dinactin, trinactin, and tetranactin, each member of the series differing from the previous one by only one methyl group. Measurements of the amplitude and time constant of the current relaxation after a voltage jump over a large domain of voltage and permeant ion concentration, together with a computer curve-fitting procedure, have allowed us, without the help of steady-state current-voltage data, to deduce and compare the values of the various rate constants for ion transport: formation (kRi) and dissociation (kDi) of the ion-carrier complex at the interface, translocation across the membrane interior of the carrier (ks) and the complex (kis). With the additional information from steady-state low-voltage conductance measurements, we have obtained the value of the aqueous phase-membrane and torus-membrane partition coefficient of the carrier (gammas and gammas). From nonactin to tetranactin with the NH4+ ion, kis, and gammas are found to increase by factors of 5 and 3, respectively, kDi and gammas to decrease respectively by factors 8 and 2, while kRi and ks are practically invariant. Nearly identical results are found for K+, Rb+, and Tl+ ions. kRi, ks and kis are quite invariant from one ion to the other except for Tl+ were kRi is about five times larger. On the other hand, kDi depends strongly on the ion, indicating that dissociation is the determining step of the ionic selectivity of a given carrier. The systematic variations in the values of the rate constants with increasing methylation are interpreted in terms of modification of energy barriers induced by the carrier increasing size. Within this framework, we have been able to establish and verify a fundamental relationship between the variations of kis and kDi with methylation.