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Abstract

The cation permeability of the cortical thick ascending limb of Henle's loop was investigated with electrophysiological methods in the isolated perfused tubule preparation of rabbit kidney. The transepithelial specific resistance (R_T) and electrical potential difference (PD) were determined in 4 experimental groups. In group 1 (n=51) the tubules were perfused with a modified Ringer's solution on both sides of the epithelium; the PD was 7±0.4 mV lumen positive, and the R_T 34±2 Ω·cm2. In group 2 (n=12) one of both sides of the epithelium was perfused with dilute (54 mmol/l) NaCl solutions under control conditions and in the absence of active transport. Inhibition was obtained in four different ways: low temperature (22° C), zero K⁺ solutions on both sides of the epithelium, 5·10⁻⁵ mol/l furosemide, added to lumen perfusate, or 10⁻⁵ mol/l ouabain added to the bathing solution. In the presence and in the absence of active transport a NaCl gradient of 154 versus 54 mmol/l induced diffusion potentials across the epithelium which were symmetrical and of nearly equal magnitude: +12, −14 and +15, −14 mV respectively. In group 3 (n=51) Na⁺ was completely replaced by choline⁺, tetraethylammonium⁺, tris-hydroxymethyl-aminomethane⁺, or Li⁺ in either bath or lumen perfusate or in both perfusates. The biionic diffusion potentials were symmetric; the replacement of Na⁺ by these cations on both sides markedly increased R_T. Both kinds of measurements yielded a permeability sequence of P_Na⁺ > P_Li⁺ > P_{organic cation}. In group 4 (n=17) 50 mmol/l of Na⁺ was replaced by K⁺, Li⁺, Rb⁺, or Cs⁺ on one of the sides and active transport was inhibited by furosemide or ouabain. From the membrane diffusion potentials and the R_T values in group 4 as well as in group 3 the following cation permeability sequence was calculated P_K⁺ > P_Na⁺ > P_Rb⁺ = P_Li⁺ > P_Cs⁺ > P_{organic cation}. It is concluded that the cortical thick ascending limb of Henle's loop has a low resistance pathway which is cation selective similar to that of “leaky” epithelia. Since the membrane diffusion potentials are symmetric and since they are not altered by inhibition of active transport, it is likely that this low resistance pathway is formed by a paracellular shunt.