Single-file diffusion multi-ion mechanism of permeation in paracellular epithelial channels.

The transepithelial fluxes, conductances and permeabilities of Li+, Na+, K+, Cs+, NH4+ and H3CNH3+ were studied under ionic concentrations ranging from 12 to 250 mM in Bufo arenarum gallbladders. When these measurements are carefully corrected in order to get only the component due to the paracellular cation channels, the following results are obtained: (1) The permeability ratios (cationic/anionic) are a decreasing function of salt concentration. (2) The partial conductances through paracellular cationic channels show nonlinear saturable concentration kinetics. (3) Moreover, partial conductance kinetics of K+, Cs+ and NH4+ present a maximum followed, at higher concentrations, by a negative-slope region. (4) The selectivity sequences obtained from biionic potentials do not agree with those obtained from partial conductance measurements. (5) The unidirectional 22Na tracer flux (serosal to mucosal) is inhibited by 63% when the K+ symmetrical concentration in the bathing solutions is raised from 25 to 200 mM. (6) When the unidirectional 42K fluxes (serosal to mucosal) at 200 mM KCl Na-free solutions are compared with K+ partial conductance by means of the Hodgkin and Keynes (Hodgkin, A.L., Keynes, R.D. 1955, J. Physiol London 128:61-88) expression, the n' factor is 2.0. These results indicate that cations do not follow the independence principle and behave as in single-file diffusion multi-ion pores when crossing the paracellular cation channels of Bufo arenarum gallbladder epithelium.