NaCl transport in mouse medullary thick ascending limbs. I. Functional nephron heterogeneity and ADH-stimulated NaCl cotransport

Abstract

We assessed the effects of antidiuretic hormone and cyclic adenosine monophosphate (cAMP) analogues on transepithelial voltage, Ve, and/or net chloride absorption in isolated mouse medullary (mTALH) and cortical (cTALH) thick ascending limbs of Henle; the passive NaCl permeability characteristics and electrical properties of the mTALH; and the effects of anion and cation substitutions and transport inhibitors on both basal and ADH-stimulated Ve and/or net chloride absorption in the mTALH. The data demonstrate that these two segments are functionally heterogeneous: ADH, at concentrations comparable to plasma levels seen in mammalian species during ordinary antidiuresis, and/or cAMP increase three- to fourfold the rate of NaCl absorption in the mTALH but not in the cTALH. The ion substitution and inhibitor data are consistent with the view that NaCl absorption in the mTALH depends on a secondary active transport process: NaCl entry across luminal membranes is a coupled process of indeterminate stoichiometry that is driven by the transmembrane electrochemical gradient for Na+, which is maintained by Na+-K+-ATPase. Finally, the data demonstrate that the mTALH is electrically leaky whether measured electrically, 11 omega . cm2, or isotopically, 50 omega . cm2, but essentially water impermeable; and that the mTALH is perm-selective for Na+ with respect to Cl-. The disparity between electrical resistances measured directly with respect to those calculated from tracer fluxes, together with the hybrid characteristics of mTALH junctional complexes (leaky to Na+ and Cl-; tight to water), may be reconciled by assuming that mTALH junctional complexes contain passive ion permeation pathways composed of narrow channels through which ions pass in single-file fashion.

CO2-stimulated NaCl absorption in the mouse renal cortical thick ascending limb of Henle. Evidence for synchronous Na +/H+ and Cl-/HCO3- exchange in apical plasma membranes.

“…One set of conclusions consistent with the present experimental data affirms the view (Hebert et al ., 1981 a) that the cTALH and mTALH of mouse kidney exhibit significant functional heterogeneity, despite the fact that these two nephron segments also share a number of common transport characteristics .…”

“…In the mouse mTALH, the combination (C02 + HC03) has no effect on either net salt absorption or the spontaneous transepithelial voltage (Hebert et al, 1981a) ; but both of these variables are enhanced significantly by ADH or by CAMP analogues (Hall and Varney, 1980 ;Hebert et al ., 1981 a), and ADH stimulates selectively adenyl cyclase activity in the mTALH (Morel, 1981) . Thus, as argued previously (Hebert et al ., 1981a, b, c), ADHmediated enhancement of net salt absorption in the mTALH may be a significant factor in determining the degree of hypertonicity of the in vivo renal medullary interstitium, and hence in regulating the degree to which urine is concentrated .…”

“…The techniques used for studying transport processes in single in vitro microperfused mouse cTALH segments were similar to those described originally by Burg et al (1966;Burg and Green, 1973) for isolated rabbit nephron segments and to those used in this laboratory (Hebert et al, 1981 a) for the study oftransport processes in segments of mouse mTALH. Stated briefly, 20-30-d-old (^-25 g) male Swiss white mice were killed by cervical dislocation and rapid exsanguination.…”

Histochemical study on the ouabain-sensitive potassium-dependent p-nitrophenyl phosphatase activity along the nephron in several mammals.

“…However, the boundary where these differences occur remains obscure. Largely for convenience, the transition from MTALH to CTALH is defined anatomically as that region of the cortico-medullary junction (3,17,22,35). However, staining features of K-NPPase reported herein suggest that medullary thick ascending limb can be divided into an inner stripe segment in which K-NPPase activity is greatest and uniformly present and an outer stripe segment in which this enzyme activity decreases gradually as it extends upward to the cortex.…”

“…Recently, physiological differences regarding the handling of sodium and water have been revealed between the cortical and medullary segments of thick ascending limbs (7,8,17) . The medullary segments appear to reabsorb sodium chloride more rapidly than the cortical segment.…”