Physical origin of Na+/Cl− selectivity of tight junctions between epithelial cells. Nonlocal electrostatic approach

Tight junctions (TJs) of epithelial cells play a key role in regulation of the ion exchange between NaCl solutions separated by the layer of these cells. Their functioning is based on a strong difference in the permeabilities of these channels for Na+ and Cl− ion migrational fluxes owing to specific properties of the protein network inside TJs. It has been assumed in this study that this phenomenon originates from combination of two effects related to this specific TJ protein (claudin) which segments are partially located inside the TJ space. First, their ionogenic groups create a negative charge distributed inside TJs, thus inducing a difference between the Na+ and Cl− concentrations inside this spatial region. Second, the effect of these negative charges is greatly enhanced owing to high energetic barriers for penetration of both ions into TJs from the external aqueous solution, due to a significantly lower values of their solvation energies inside this spatial region, compared to the aqueous solution. This effect has been attributed to the change of the nonlocal dielectric response of the polar medium inside the TJ region where the long-range water structure is modified by the contact with segments of claudin molecules distributed in this space. Acting together, these two factors lead to pronounced permselectivity of TJs with respect to singly-charged cations and anions, i.e. to much higher Na+ concentration inside TJs, compared to the Cl− one. Derived expressions for the resolvation energies of ions as well as for their concentrations inside the TJ region on the basis of electrostatics of nonlocal dielectric media have been applied for interpretation of experimental data for the Na+/Cl− selectivity of such channels. •Observed Na+/Cl− selectivity of tight junctions (TJs) between epithelial cells has been interpreted.•High values of the selectivity originate from the dual role of claudin proteins distributed inside TJs.•Distributed proteins change the long-range dielectric response of water and ion solvation energies inside TJs.•Large negative values of Na+ and Cl− resolvation energies lead to their low concentrations inside TJs.•Strong Na+/Cl− selectivity of TJs is due to low ionic concentrations combined with negative claudin charges inside TJs.