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Nitrogenous cations as probes of permeation channels

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Summary

Nitrogenous cations may provide information-rich probes of cation-selective channels. Hence, for 52 nitrogenous cations we have used dilution potentials and biionic potentials to measure relative permeability coefficients (P's) across gallbladder epithelia of frog and rabbit, and have also determined the free-solution mobilities. MeasuredP's of most cations are uninfluenced by the presence of the neutral form. The main permeation pathway for most hydrophilic cations is across the tight junctions.P's decrease with molecular size and increase with number of donor protons available for hydrogen-bond formation. Selectivity isotherms have been constructed from variation inP's due to pH or due to differences among individual animals. Both types of variation are consistent with the pattern expected from variation in electrostatic field strength of cation-binding sites. The isotherms permitP's to be re-expressed in a way that largely eliminates effects of species differences in field strength. Remaining species differences inP's are well fitted by a model of steric restriction, provided that one takes into account the effect of hydrogen bonding on molecular size. Rabbit gallbladder behaves as if it has narrower permeation channels than frog gallbladder. After correction for these steric effects,P is found to increase with number of donor protonsn H up to four protons, with a steeper slope in rabbit than in frog gallbladder, but is independent ofn H from four to at least nine. Two groups of cations appear to permeate significantly via pathways other than tight junctions: oxycations, via polar pathways in epithelial cell membranes of rabbit but not frog gallbladder; and lipid-soluble cations, via membrane lipid.

The results suggest that the cation-binding sites of gallbladder tight junction are acidic proton-acceptors that discriminate more sharply among proton donors than does water. Proton-rich solutes tend to be more permeant for two reasons: stronger binding energies to membrane proton-acceptor sites, and smaller effective size in a proton-acceptor environment. As deduced from comparisons of nitrogenous cation selectivity patterns, the permeation channel through gallbladder tight junction differs from nerve's sodium channel and artificial carriers and channels in its higher hydration and lower range of selectivity. Based on the steric analysis of nitrogenous cation permeation, one can correct alkali cation permeability coefficients for the effect of steric restriction.

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  1. Julio H. Moreno

    Present address: Instituto de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina

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  1. Physiology Department, UCLA Medical School, 90024, Los Angeles, California

    Julio H. Moreno & Jared M. Diamond

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Moreno, J.H., Diamond, J.M. Nitrogenous cations as probes of permeation channels. J. Membrain Biol. 21, 197–259 (1975). https://doi.org/10.1007/BF01941070

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