Moreno J H, Diamond J M
J Membr Biol. 1975;21(3-4):197-259. doi: 10.1007/BF01941070.
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. Measured P's of most cations are uninfluenced by the presence of the netral 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 in P'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 permit P's to be re-expressed in a way that largely eliminates effects of species differences in field strength. Remaining species differences in P'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 protons nH up to four protons, with a steeper slope in rabbit than in frog gallbladder, but is independent of nH 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.
含氮阳离子可为阳离子选择性通道提供信息丰富的探针。因此，对于52种含氮阳离子，我们利用稀释电位和双离子电位来测量蛙和兔胆囊上皮的相对渗透系数（P值），并确定了其在自由溶液中的迁移率。大多数阳离子的测量P值不受中性形式存在的影响。大多数亲水性阳离子的主要渗透途径是通过紧密连接。P值随分子大小减小而增大，随可用于形成氢键的供体质子数量增加而增大。通过因pH值变化或个体动物间差异导致的P值变化构建了选择性等温线。这两种类型的变化都与阳离子结合位点静电场强度变化所预期的模式一致。这些等温线使P值得以重新表达，从而在很大程度上消除了场强物种差异的影响。如果考虑氢键对分子大小的影响，剩余的物种间P值差异可通过空间位阻模型得到很好的拟合。兔胆囊的行为表现为其渗透通道似乎比蛙胆囊的更窄。校正这些空间位阻效应后，发现P值随供体质子数量nH增加至四个质子而增大，兔胆囊中的斜率比蛙胆囊中的更陡，但从四个质子到至少九个质子时P值与nH无关。两组阳离子似乎通过紧密连接以外的途径显著渗透：氧鎓阳离子，通过兔而非蛙胆囊上皮细胞膜中的极性途径；以及脂溶性阳离子，通过膜脂质。结果表明，胆囊紧密连接的阳离子结合位点是酸性质子受体，与水相比，它们对质子供体的区分更为敏锐。富含质子的溶质往往更易渗透，原因有二：与膜质子受体位点的结合能更强，以及在质子受体环境中的有效尺寸更小。从含氮阳离子选择性模式的比较推断，通过胆囊紧密连接的渗透通道在更高的水合作用和更低的选择性范围方面不同于神经的钠通道以及人工载体和通道。基于含氮阳离子渗透的空间位阻分析，可以校正碱金属阳离子渗透系数的空间位阻效应。
