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S C Hebert

Publications and source records attributed to S C Hebert.

154 records · Page 9Linked to original sources
PubMed1984

Control of NaCl transport in the thick ascending limb.

The mammalian renal thick ascending limb of Henle serves to dilute the urine and supply energy for countercurrent multiplication as a consequence of its ability to absorb NaCl in excess of water. During the past few years our notions of the mechanism of and the factors that control NaCl absorption by the thick ascending limb of Henle have been altered substantially. This review presents evidence for a model of NaCl absorption in the thick ascending limb in which net Cl- absorption is rheogenic and involves a secondary active transport process. According to this model, net Cl- absorption occurs via a furosemide-sensitive coupled electroneutral (1Na+, 1K+, 2Cl-) apical Cl- entry mechanism in parallel with a large K+ conductance in apical plasma membranes and a conductive Cl- exit mechanism in basolateral plasma membranes. The lumen-positive voltage and high paracellular conductance in the thick ascending limb provides a means of driving 50% of net Na+ absorption through the paracellular route and reduces, with respect to exclusively transcellular active Na+ absorption, the metabolic energy expenditure for net Na+ absorption. In some mammalian species, ADH may enhance the rate of NaCl absorption in the medullary thick ascending limb by directly increasing the functional number of (1Na+, 1K+, 2Cl-) cotransport units as well as the K+ conductance unit in apical plasma membranes and by indirectly increasing basolateral membrane Cl- conductance. This latter effect on basolateral Cl- conductance may be secondary to a hormone-induced increase in cell Cl- activity. The ADH-dependent increase in NaCl absorption can be modified directly by both prostaglandin E2 and peritubular hypertonicity. During antidiuresis these hormonal and nonhormonal modulations of NaCl absorption may provide a number of feedback systems that control the level of interstitial osmolality and, as a consequence, concentrating power without affecting net NaCl absorption.

Animals↗
PubMed1982

Carbonic anhydrase histochemistry in rabbit and mouse kidneys.

The presence of carbonic anhydrase activity in rabbit and mouse kidneys was examined using a histochemical procedure with plastic embedded sections stained by the modified version of the cobalt-phosphate method (Hansson, 1967, 1968; Ridderstrale, 1976). Proximal convoluted tubules (S1 and S2 segments) in both species were strongly positive for carbonic anhydrase activity on the membranes of the luminal, lateral, and basal surfaces. The apical cytoplasm beneath the brush border and the nuclei also stained positively for carbonic anhydrase. The S3 segment (pars recta) of the proximal tubule in the rabbit was positive on the luminal membrane, with somewhat less intensity seen on the lateral and basal surfaces. This segment in the mouse was completely negative. The first part of the thin limbs of long-looped nephrons exhibited strong staining in the mouse. Faint luminal staining was present on descending thin limbs of short-looped nephrons in the mouse. In the rabbit, both the medullary and cortical ascending thick segments of the limb of Henle were completely negative. In contrast, the medullary and cortical ascending thick limbs in the mouse kidney showed staining on all plasma membranes. The intercalated cells in the cortical and medullary portion of the collecting tubules stained positively for carbonic anhydrase in both species. The principal cells of the collecting duct in the cortex were negative in the rabbit and faintly positive in the mouse. The principal cells in the upper medullary collecting tubules in both species stained intensely along the luminal, lateral, and basal cell membranes. The papillary collecting ducts were largely negative in both the rabbit and the mouse. Some interstitial cells in the rabbit in the region of the papillary tip were strongly positive. We conclude that there is a marked difference in carbonic anhydrase activity within and between the renal tubular segments of the rabbit and the mouse. In addition, these distinct differences that exist between the two species correlated with known physiological roles in ion transport.

Animals↗
PubMed1981

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

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.

Amiloride↗
PubMed1981

NaCl transport in mouse medullary thick ascending limbs. II. ADH enhancement of transcellular NaCl cotransport; origin of transepithelial voltage.

We measured the relations between tubular perfusion rate and the rate of net NaCl transport in medullary thick ascending limbs of Henle (mTALH) either in the presence or absence of ADH. These data, together with the known Na+, Cl-, and water permeability characteristics of the mTALH, were used to calculate tau NaCl (mol . s-1 . cm-2), the rate of conservative Cl- transport from lumen through cells to interspaces; and CNaCl, the effective NaCl concentration in lateral intercellular spaces. The experimental results indicate that in these tubules the rate of net Cl- absorption increases monotonically with perfusion rate, and that at a given perfusion rate ADH increases the rate of net salt absorption. The theoretical calculations show clearly that the ADH-mediated increase in salt absorption depends on an increase in the rate of conservative transcellular Cl- transport. However, the present analytical data do not permit a distinction between wholly electroneutral apical membrane NaCl entry with respect to a process in which apical membrane Na+/Cl- entry has a stoichiometry less than unity, and electrogenic Na+ transport accounts for the remaining component of net Na+ absorption. Identification of the stoichiometry of the Na+/Cl- apical membrane entry step will depend, among other factors, on identifying explicitly the diffusion resistance of paracellular fluid and the mode of passive ion transport across junctional complexes.

Animals↗
PubMed1981

NaCl transport in mouse medullary thick ascending limbs. III. Modulation of the ADH effect by peritubular osmolality.

We evaluated the effects of increasing bath osmolality on both the passive permeability properties and the ADH-dependent rates of net Cl- absorption in isolated mouse medullary thick ascending limbs of Henle (mTALH). Increases in both osmolality to 900 mosmol/kg H2O with 600 mM urea had no effect on either the electrical (PNa/PCl ratio, 1.7 and 1.9 with and without peritubular urea, respectively) or tracer (PNa, 0.21 and 0.22 micrometers . s-1 with and without peritubular urea, respectively) ionic permeability characteristics of the mTALH. However, this degree of urea bath hypertonicity reduced reversibly both JnetNaCl, the net rate of transepithelial NaCl absorption, and Ve, the spontaneous transepithelial voltage: JnetNaCl fell by 85% and Ve by 70%. Both of these latter effects could be accounted for quantitatively by an 85% reduction in tau NaCl, the rate of conservative transcellular NaCl transport. The inhibition of Ve by peritubular medium urea hypertonicity was not altered by supramaximal bath concentrations of ADH, supramaximal bath concentrations of cAMP analogues, or symmetrical addition of urea to perfusate and bath. Increases in peritubular medium mannitol concentrations also reduced Ve; the inhibition of Ve was not reversed by supramaximal bath concentrations of aDH. Cell volume remained unchanged with peritubular urea but was reduced by peritubular mannitol. These data indicate that in the mTALH increases in bath osmolality with nonelectrolytes inhibit tau NaCl noncompetitively with respect to ADH or cAMP and independently of cell volume. JnetCl was also reduced with increases in peritubular medium NaCl concentration and was associated with a reduction in cell volume.

Animals↗
PubMed1980

Interactions of temperature and ADH on transport processes in cortical collecting tubules.

We evaluated the temperature dependence of the permeability coefficients for ADH-independent and ADH-dependent zero volume flow diffusion of THO (PDw, micron/s), for ADH-dependent zero volume flow diffusion of the highly lipophilic solute n-[3H]butanol (PDb, micron/s), and for ADH-dependent lumen-to-bath osmosis (Pf, micron/s) in rabbit isolated cortical collecting tubules. The ADH-dependnet Pf and PDw data are consistent with the hypothesis that water crosses the apical plasma membranes of these tubules through narrow aqueous channels by single-file diffusion; and using the raw temperature-dependent data, we calculate that these channels contain congruent to six H2O molecules per channel, both in the presence and in the absence of ADH. Apparent activation energies (EA, kcal/mol), as an upper estimate of the true activation energies, were calculated for these transport processes. The EA for osmosis for 6-23 degrees C, 9.7 +/- 1.1 kcal/mol, was indistinguishable from that reported previously for 23-37 degrees C either in the presence of absence of ADH, and from the ADH-independent EA for THO diffusion, 10.11 +/- 0.68 kcal/mol, measured in the range 15-37 degrees C. We interpret these data to indicate that in the absence of ADH THO diffusion at zero volume flow is hindered primarily by the same sites, narrow channels in apical membranes. The apparent EA for ADH-dependent zero volume flow THO diffusion, 5.11 +/- 0.40 kcal/mol, measured over the temperature range 6-38 degrees C, is approximately half the apparent EA for osmosis in the presence or absence of ADH and ADH-independent THO diffusion. The former value, when corrected for diffusion constraints in series with apical plasma membranes, becomes indistinguishable from the latter values. These date are consistent with the possibility that two factors contribute to the ADH-mediated disparity between Pf and PDw in these tubules: cytosolic diffusion constraints that impede ADH-dependent THO diffusion but not osmotic volume flow, and narrow aqueous channels as the primary route for water flux through apical plasma membranes. Finally, the EA for n-butanol diffusion shows a break in the Arrhenius plot. Above 23 degrees C, the EA is 4.77 +/- 0.77 kcal/mol and n-butanol diffusion is impeded primarily by the cytosol. Below 23 degrees C, the EA rises to approximately 9 kcal/mol because the hydrophobic regions of apical plasma membranes contribute an increasing fraction of the total resistance to n-butanol diffusion.

Animals↗