ANOMALOUS MOLE FRACTION EFFECT, ELECTROSTATICS, AND BINDING IN IONIC CHANNELS

Ionic channels bathed in mixed solutions of two permeant electrolytes often conduct less current than channels bathed in pure solutions of e ither. For many years, this anomalous mole fraction effect (AMFE) has been thought to occur only in single-file pores containing two or more ions at a time. Most thinking about channels incorporates this view. We show here that the AMFE arises naturally, as an electrostatic conse quence of localized ion specific binding, if the average current throu gh a channel is described by a theory (Poisson-Nernst-Planck, NP) that computes the average electric field from the average concentration of charges in and near the channel. The theory contains only those ion-i on interactions mediated by the mean field, and it does not enforce si ngle filing. The AMFE is predicted by PNP over a wide range of mean co ncentrations of ions in the channel; for example, it is predicted when (on the average) less, or much less, than one ion is found in the cha nnel's pore. In this treatment, the AMFE arises, in large measure, fro m a depletion layer produced near a region of ion-specific binding. Th e small excess concentration of ions in the binding region repels all nearby ions of like charge, thereby creating a depletion layer. The ov erall conductance of the channel arises in effect from resistors in se ries, one from the binding region, one from the depletion zone, and on e from the unbinding region. The highest value resistor (which occurs in the depletion zone) limits the overall series conductance. Here the AMFE is not the result of single filing or multiple occupancy, and so previous views of permeation need to be revised: the presence of an A MFE does not imply that ions permeate single file through a multiply o ccupied pore.