1 Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021; and 2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
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ABSTRACT |
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The role of epithelial Na channels in the response of the
kidney to short-term Na deprivation was studied in rats. Animals were
fed either a control-Na (3.9 g/kg) or a low-Na ( 3.8 mg/kg) diet for
15 h. Urinary excretion of Na (µmol/min), measured in conscious
animals in metabolic cages, was 0.45 ± 0.07 in controls and
0.04 ± 0.01 in Na-deprived animals. Glomerular filtration rate,
measured as the clearance of creatinine, was unaffected by the change
in diet, suggesting that the reduced Na excretion was the result of
increased Na reabsorption. K excretion (µmol/min), increased after
the 15-h period of Na deprivation from 0.70 ± 0.10 to 1.86 ± 0.19. Thus the decrease in urine Na was compensated for, in terms of
electrical charge balance, by an increase in urine K. Plasma
aldosterone increased from 0.50 ± 0.08 to 1.22 ± 0.22 nM.
Principal cells from cortical collecting tubules isolated from the
animals were studied by using the patch-clamp technique. Whole cell
amiloride-sensitive currents were negligible in the control group
(5 ± 4 pA/cell) but substantial in the Na-deprived group
(140 ± 28 pA/cell). The abundance of the epithelial Na channel subunits, ,
, and
in the kidney was estimated by using
immunoblots. There was no change in the overall abundance of any of the
subunits after the 15-h Na deprivation. However, the apparent molecular mass of a fraction of the
-subunits decreased as was previously reported for long-term Na deprivation. Calculations of the rate of Na
transport mediated by the Na channels indicated that activation of the
channels during short-term Na deprivation could account in large part
for the increased Na reabsorption under these conditions.
cortical collecting tubule; epithelial sodium channel; aldosterone; sodium transport; potassium transport
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INTRODUCTION |
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THE RENIN-ANGIOTENSIN-ALDOSTERONE axis is thought to play an important role in the regulation of Na balance and plasma volume (8). A reduction in plasma volume triggers the release of renin from juxtaglomerular cells, stimulating production of angiotensin from angiotensinogen and ultimately leading to increased circulating levels of aldosterone. An important target of aldosterone action on the kidney is the epithelial Na channel (ENaC) (23). Chronic elevation of plasma aldosterone has been shown to increase amiloride-sensitive Na transport in the isolated-perfused cortical collecting tubule (CCT) (21, 26, 29) and to increase amiloride-sensitive short-circuit current in the colon (2, 32). In the rat kidney, aldosterone increases the density of conducting Na channels in the apical membrane of the CCT (17). The increase can be dramatic, starting from an undetectably low number when animals are on a diet of normal rat chow and reaching three to five channels per patch when the rats are fed a low-salt diet for a week or more. More rapid effects of aldosterone at the single-channel level have been observed in vitro by using the A6 cell line (11). In this case increased channel activity is due at least in part to an increase in open probability.
The role of aldosterone-mediated activation of Na channels in the day-to-day regulation of sodium excretion is not so well documented. Infusion of aldosterone in vivo can reduce Na excretion within 1-2 h (10), although the mechanisms through which this occurs have not been delineated. In addition to activation of Na channels, aldosterone has been shown to stimulate NaCl cotransporter in the distal convoluted tubule (12) and to alter Na/H exchange in Madin-Darby canine kidney cells through a nongenomic pathway (15). In previous studies on the rat CCT, our laboratory could not document a clear elevation of either Na channel activity or plasma aldosterone levels for periods of Na deprivation of less than 48 h (17). Thus, although the regulation of Na channels by aldosterone has been extensively studied, the relevance of this pathway in the day-to-day maintenance of Na homeostasis is less well established.
In the present study we have reevaluated this question by measuring changes in Na and K excretion as well as levels of Na channel activity and plasma aldosterone in rats that have been fed a low-Na diet for short periods of time. We found that the appearance of channel activity correlates well with the fall in Na excretion, and that the magnitude of the increase can account in large part for the increased rate of Na reabsorption by the nephron.
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METHODS |
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Animals. Sprague-Dawley rats of either sex (100-150 g) raised free of viral infections (Charles River Laboratories, Kingston, NY) were fed with either a low-Na diet (Na content 3.8 mg/kg; K content 8.6 g/kg; ICN, Cleveland, OH) or a control diet (3.9 g/kg Na, 6.4 g/kg K, Harlan-Teklad, Madison, WI). The food intake per rat ranged between 6 and 15 g/day. A different group of animals were implanted subcutaneously with osmotic minipumps (model 2002 or 1007D Alza, Palo Alto, CA) to increase levels of circulating aldosterone. Aldosterone was dissolved in polyethylene glycol 300 at concentrations calculated to give the desired infusion rate according to the pumping rate specified by the manufacturer. These rats were fed a control diet.
To measure urinary excretion rates animals were kept in a metabolic cage (Nalge Nunc International, Rochester, NY) for 2-3 h without food but with free access to drinking water, lightly sweetened with 3% sucrose, to increase water intake and urine flow.Analytical methods. Rats were anesthetized with methoxyflurane, and blood was obtained from the abdominal aorta. Na and K were measured in plasma and in urine by flame photometry (model 943, Instrumentation Laboratory, Lexington, MA).
Creatinine was measured by an enzymatic method (6). Only female rats were used for creatinine clearance measurements because creatinine is not secreted by the kidney in the female rat (9). Radioimmununoassay for plasma aldosterone was carried out with the ImmuChem double antibody kit from ICN (ICN Pharmaceuticals, Costa Mesa, CA) as described previously (19).Whole cell currents. After the animals were killed, the kidneys were removed, and CCTs were dissected free and opened manually to expose the luminal surface. Under these conditions the tissues retain their epithelial structure and the cells are presumed to remain polarized. The split tubules were attached to a small plastic rectangle coated with Cell-Tak (Collaborative Research, Bedford, MA) and placed in a perfusion chamber mounted on an inverted microscope. The chamber was continuously perfused with solution consisting of (in mM) 135 Na methane sulfonate, 5 KCl, 2 CaCl2, 1 MgCl2, 2 glucose, 5 mM BaCl2, and 10 HEPES, adjusted to pH 7.4 with NaOH, and prewarmed to 37°C.
Principal cells of the tubule were identified visually. The patch-clamp pipettes were filled with solutions containing (in mM) 7 KCl, 123 aspartic acid, 20 CsOH, 20 tetraethylammonium hydroxide, 5 EGTA, 10 HEPES, 3 MgATP and 0.3 guanosine 5'-O-(2-thiodiphosphate) with the pH adjusted to 7.4 with KOH. Basic protocols for measuring whole cell amiloride-sensitive current were previously described (18, 20).Antibodies.
This study utilized rabbit polyclonal antibodies directed to the -,
-, and
-subunits of the rat ENaC (14) and the
Na-K-2Cl cotransporter (BSC1/NKCC2) (12).
Semiquantitative immunoblotting. To compare sodium transporter protein abundance between groups of rats, semiquantitative immunoblotting was utilized. The procedure has been described in detail previously (12, 28). Briefly, the kidneys were homogenized intact, by using a tissue homogenizer (Omni 1000 fitted with a micro-sawtooth generator) in ice-cold isolation solution containing 250 mM sucrose/10 mM triethanolamine (Calbiochem, La Jolla, CA) with 1 µg/ml leupeptin (Bachem California, Torrance, CA) and 0.1 mg/ml phenylmethylsulfonyl fluoride (US Biochemical, Toledo, OH). Total protein (Pierce BCA kit) was measured and the samples were solubilized at 60°C for 15 min in Laemmli sample buffer. SDS-PAGE was performed on 7.5, 10, or 12% polyacrylamide gels. To confirm equal loading among samples, an initial gel was stained with Coomassie blue as described previously (28). For immunoblotting, the proteins were transferred electrophoretically from unstained gels to nitrocellulose membranes. The membranes were blocked with 5 g/dl nonfat dry milk for 30 min, probed with the respective primary antibodies overnight at 4°C, and then probed with secondary antibody (donkey anti-rabbit immunoglobulin G conjugated with horseradish peroxidase, Pierce no. 31458, diluted to 1:5,000) for 1 h at room temperature. The sites of antibody-antigen reaction were visualized by using enhanced chemiluminescence substrate (LumiGLO for Western blotting, Kirkegaard and Perry no. VC110) before exposure to X-ray film (Kodak no. 165-1579). The band densities were quantitated by laser densitometry (Molecular Dynamics model PDS1-P90). Image Quant version 5.0 software was used to determine the background correction and quantify the final band densities. The densitometry values were normalized to facilitate comparisons, defining the mean for the control group as 100%. Statistical analysis used either an unpaired t-test or Welch t-test.
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RESULTS |
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Rats were kept overnight on either a control or low-Na diet. After
15 h the animals were transferred to metabolic cages without food
but with free access to drinking water. Normally the rats eat little
food during the late morning hours, so we presume that the food
deprivation has a minimal effect on overall salt balance. Urine was
collected over a 2- to 3-h period. The effect of the low-sodium diet on
excretion rates is shown in Table 1.
Compared with matched controls, sodium excretion is reduced by more
than 90%.
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In principle, a reduction in Na excretion can result from either a reduction in the filtered Na load or from an increase in Na reabsorption along the nephron. To evaluate the impact of changes in filtered load we estimated GFR by using the creatinine clearance. Urinary creatinine was measured over the same 2- to 3-h period described above, whereas plasma creatinine was measured on a sample of blood obtained from the aorta when the rat was killed at the end of this period. The results are shown in Table 1. The low-Na diet did not significantly change GFR after 15 h. Therefore, the decreased Na excretion is most likely due to an increase in Na reabsorption by the kidney. There was a tendency for GFR to decrease after long-term Na deprivation (Table 1), but this did not reach statistical significance (P > 0.2).
In most nephron segments, reabsorption of Na is accompanied by a parallel reabsorption of Cl. The major exception is in the CCT in which uptake of Na is coupled electrically with the secretion of K and H ions. We therefore compared changes in K and Na excretion as a first test for whether the CCT might be involved in the increased reabsorption rate. As shown in Table 1, K excretion increased after 15 h on a low-Na diet. In fact, the increase in K excretion consistently exceeded the decrease in Na excretion. We interpreted these data as indicating that nephron segments in which Na is effectively exchanged for K, most likely including the CCT, are involved in the alteration of electrolyte handling under these conditions.
To evaluate whether increased mineralocorticoid secretion by the
adrenals could play a role in the sodium retention, we measured levels
of aldosterone in the plasma of rats that were Na depleted for 15 h. As indicated in Table 2, aldosterone
levels increased modestly from 18 to 44 ng/dl or 0.50 to 1.22 nM. This increase was statistically significant but much
smaller than that observed after chronic Na depletion (Table 2, see
also Refs. 18, 20).
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To test whether this increase in circulating aldosterone could be
sufficient to activate Na channels, CCTs were dissected from control
and 15-h Na-deprived rats. The tubules were split open, and Na channel
activity was assessed as the whole cell amiloride-sensitive current.
Figure 1 shows typical current-voltage
relationship curves in the presence and absence of amiloride for the
two conditions. In tubules from control animals there was little or no
effect of amiloride on the electrical properties of the principal
cells. Changes in current of >50 pA at a cell potential of 100
mV were observed in only 2 of 28 cells (Fig.
2). In contrast, in tubules from
Na-deprived animals significant amiloride-sensitive currents (INa) were recorded in 18 of 27 cells. The mean
value was 140 pA/cell at
100 mV. This represents one-third to
one-fourth of that seen in tubules from chronically Na-depleted rats
(Table 2). As shown in Fig. 2 there was a substantial variation in the INa values.
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These data were compared with those obtained by infusing aldosterone through osmotic minipumps to give comparable levels of the hormone over a comparable period of time. The aldosterone infusion resulted in slightly higher hormone levels (1.72 vs. 1.22 nM), whereas the INa values were somewhat lower (93 vs. 142 pA/cell). This suggests that increased aldosterone can account in large part for the observed Na channel activity.
Previous studies indicated that biochemical alterations in ENaC
subunits were associated with stimulation of Na channel activity. These
included an increase in the abundance of the -subunit protein, and a
shift in the apparent molecular mass of the
-subunit to lower levels
(14). We tested whether either of these parameters correlated with the decreased Na excretion that we observed with the
15-h depletion protocol. Figure 3 shows
an immunoblot in which samples of kidney from the same animals used for
the excretion and electrophysiological measurements were probed with
antibodies raised against the three different ENaC subunits. Similar
blots made with kidneys from chronically Na-depleted rats are shown for
comparison (Fig. 4). There was no
significant change in the abundance of the
-subunit in the 15-h
depleted animals [107 ± 24% of control; P = not
significant (NS)], whereas in those depleted for longer times higher
levels were observed (164 ± 27% of control; P < 0.05) as previously reported. For the
-subunit there was an increase
in the amount of the lower molecular mass species (60-70 kDa)
(314 ± 57% of control; P < 0.05). The
percentage of the total densitometric signal in the lower molecular
mass region was 6.2 ± 0.4% in controls and 25 ± 7%
(P < 0.05 vs. controls) for the 15-h Na-depleted rats.
Similar but more pronounced effects were seen in the chronically
depleted animals. The increase in the lower molecular mass species was
885 ± 93% of control (P < 0.05). The fraction
of the signal in the lower molecular mass region was 2.2 ± 2.3%
in controls and 44 ± 2% for the Na-depleted rats. Thus the
alterations in the
-subunit correlate well with the activation of
the channels. There was a significant heterogeneity evident in the
blots. This also corresponded reasonably well with physiological
measurements. The two animals that had the largest average
INa were also those that had the two largest
effects on the
-subunit (second and third lanes from
left, low-NaCl, Fig. 3). The rat that had the largest
percentage of low-molecular mass
-subunit (middle lane,
low NaCl, Fig. 3) also had the highest value of plasma aldosterone.
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As a negative control, samples were also probed for the bumetanide-sensitive Na-K-2Cl cotransporter (BSC1/NKCC2). There was no significant change in the protein abundance for BSC1 in samples from 15-h depleted animals (85 ± 32% of control; P = NS) or chronically depleted animals (113 ± 25% of control; P = NS), as previously shown.
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DISCUSSION |
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Time course of aldosterone action. Our results imply that the control of Na channels by aldosterone can participate in Na homeostasis during day-to-day variations in Na intake. This result is not surprising in light of the central role generally attributed to the renin-angiotensin-aldosterone axis in the control of blood volume and blood pressure. However, we consider its demonstration significant in that it is, to our knowledge, the first study to make a direct connection between channel activity and in vivo salt balance over this short time course.
In a previous study (17), our laboratory found little evidence for increased channel activity or plasma aldosterone until 48 h after the initiation of a low-Na diet regimen. We suspect that the difference may lie in the degree of Na deprivation. In the earlier protocol, several rats were housed in the same cage and during Na depletion were frequently observed drinking each other's urine. This would allow a fair degree of Na "recycling," delaying the time at which the renin-angiotensin-aldosterone system is activated. In the present study the animals were housed singly. We cannot be certain that the observed activation of Na channels is completely accounted for by increased aldosterone secretion. The rise in plasma aldosterone is significant but small. Because the concentrations are close to the reported dissociation constant values for binding to mineralocorticoid receptors [0.5-3 nM (23)], this rise will also be accompanied by a significant increase in receptor occupancy. As shown in Table 2, infusion of exogenous aldosterone to achieve similar plasma levels had an effect on INa, which was not statistically different from that achieved with Na depletion. However, the effect was, if anything, a bit smaller, and we cannot rule out the possibility that other factors are involved in regulating the channels under these circumstances.K secretion vs. Na absorption. One unexpected finding was the large increase in K excretion relative to the decrease in Na excretion during the short-term Na depletion (Table 1). It is likely that the enhanced K excretion is related to the increase in plasma K that was also observed. The reason for this increase is unclear, but it has been observed before during Na depletion (3). In the CCT, Na and K fluxes can be electrically coupled across the apical membrane and more directly coupled through the Na/K-ATPase across the basolateral membrane. It is unlikely that there can be an excess of K secretion over Na reabsorption in such a system. In the rabbit CCT, measurements over a large range of Na transport indicated a coupling ratio of K secretion to Na reabsorption of 0.74 (27). It is possible that, whereas Na/K exchange is activated in the CCT, NaCl reabsorption is inhibited at a more proximal site, increasing delivery of Na to the collecting duct. Alternatively, KCl secretion might be stimulated. The most likely site for the latter event would be the distal convoluted tubule where an electroneutral KCl cotransport is thought to contribute to transepithelial salt movement (30). Regardless of the mechanism, it is likely that enhanced K secretion is driven at least in part by the elevation in plasma K that was consistently observed with the low-Na diet (Table 1). This could be due in part to the slightly higher K content of the low-Na diet (see METHODS). We cannot rule out a contribution due to efflux of K from intracellular stores.
Biochemical events. The cellular actions of aldosterone are complex and are thought to involve the increased synthesis of key transport and/or regulatory proteins on different time scales (31). These time scales are often divided into "early" (<3 h) and "late" (>3 h) phases based on the responses of in vitro systems to an instantaneous addition of a large concentration of hormone. It is not completely clear how this relates to the in vivo response to a change in salt intake, which in the case of a reduction of dietary Na will result in a gradually increasing concentration of circulating aldosterone levels.
In the rat kidney, two effects of aldosterone on the ENaC subunit proteins have been documented. The abundance of both mRNA (1, 5, 16, 22) and protein (14) of theQuantitative assessment. To consider the quantitative impact of the stimulation of Na channel activity on the reduction of Na excretion by the kidney, we have made the following assumptions regarding transport by the CCT.
1) The apical membrane voltage is ![]() |
ACKNOWLEDGEMENTS |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-11489 and DK-27847.
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FOOTNOTES |
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Address for reprint requests and other correspondence: L. G. Palmer, Dept. of Physiology and Biophysics, Weill Medical College of Cornell Univ., 1300 York Ave., New York, NY 10021 (E-mail: lgpalm{at}med.cornell.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 6 June 2000; accepted in final form 20 September 2000.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Asher, C,
Wald H,
Rossier BC,
and
Garty H.
Aldosterone-induced increase in the abundance of Na+ channel subunits.
Am J Physiol Cell Physiol
271:
C605-C611,
1996
2.
Bastl, CP,
Binder HJ,
and
Hayslett JP.
Role of glucocorticoids and aldosterone in maintenance of colonic cation transport.
Am J Physiol Renal Fluid Electrolyte Physiol
238:
F181-F186,
1980[ISI][Medline].
3.
Boyd, JE,
Palmore WP,
and
Mulrow PJ.
Role of potassium in the control of aldosterone secretion in the rat.
Endocrinology
88:
556-565,
1971[ISI][Medline].
4.
Dørup, J.
Ultrastructure of three-dimensionally localized distal nephron segments in superficial cortex of the rat kidney.
J Ultrastruct Res
99:
169-187,
1988[ISI].
5.
Escoubet, B,
Coureau C,
Bonvalet JP,
and
Farman N.
Noncoordinate regulation of epithelial Na channel and Na pump subunit mRNAs in kidney and colon by aldosterone.
Am J Physiol Cell Physiol
272:
C1482-C1491,
1997
6.
Fossati, P,
Prencipe L,
and
Berti G.
Enzymatic creatinine assay: a new colorimetric method based on hydrogen peroxide measurement.
Clin Chem
29:
1494-1496,
1983
7.
Frindt, G,
Silver RB,
Windhager EE,
and
Palmer LG.
Feedback regulation of Na channels in rat CCT III. Response to cAMP.
Am J Physiol Renal Fluid Electrolyte Physiol
268:
F480-F489,
1995
8.
Gonzalez-Campoy, JM,
and
Knox FG.
Integrated responses of the kidney to alterations in extracellular fluid volume.
In: The Kidney: Physiology and Pathophysiology, edited by Seldin DW,
and Giebisch G.. New York: Raven, 1992.
9.
Harvey, AM,
and
Malvin RL.
The effect of androgenic hormones on creatinine secretion in the rat.
J Physiol (Lond)
184:
883-888,
1966[ISI][Medline].
10.
Horisberger, JD,
and
Diezi J.
Effects of mineralocorticoids on Na+ and K+ excretion in the adrenalectomized rat.
Am J Physiol Renal Fluid Electrolyte Physiol
245:
F89-F99,
1983
11.
Kemendy, AE,
Kleyman TR,
and
Eaton DC.
Aldosterone alters the open probability of amiloride-blockable sodium channels in A6 epithelia.
Am J Physiol Cell Physiol
263:
C825-C837,
1992
12.
Kim, GH,
Masilamani S,
Turner R,
Mitchell C,
Wade JB,
and
Knepper MA.
The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein.
Proc Natl Acad Sci USA
95:
14552-14557,
1998
13.
Knepper, MA,
Danielson RA,
Saidel GM,
and
Post SL.
Quantitative analysis of renal medullary anatomy in rats and rabbits.
Kidney Int
12:
313-323,
1977[ISI][Medline].
14.
Masilamani, S,
Kim GH,
Mitchell C,
Wade JB,
and
Knepper MA.
Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney.
J Clin Invest
104:
R19-R23,
1999
15.
Oberleithner, H,
Weigt M,
Westphale HJ,
and
Wang W.
Aldosterone activates Na+-H+ exchange and raises cytoplasmic pH in target cells of the amphibian kidney.
Proc Natl Acad Sci USA
84:
1464-1468,
1987[Abstract].
16.
Ono, S,
Kusano E,
Muto S,
Ando A,
and
Asano Y.
A low-Na+ diet enhances expression of mRNA for epithelial Na+ channel in rat renal inner medulla.
Pflügers Arch
434:
756-763,
1997[ISI][Medline].
17.
Pácha, J,
Frindt G,
Antonian L,
Silver R,
and
Palmer LG.
Regulation of Na channels of the rat cortical collecting tubule by aldosterone.
J Gen Physiol
102:
25-42,
1993[Abstract].
18.
Palmer, LG,
Antonian L,
and
Frindt G.
Regulation of the Na-K pump of the rat cortical collecting tubule by aldosterone.
J Gen Physiol
102:
43-57,
1993[Abstract].
19.
Palmer, LG,
and
Frindt G.
Regulation of apical K channels in rat cortical collecting tubule during changes in dietary K intake.
Am J Physiol Renal Physiol
277:
F805-F812,
1999
20.
Palmer, LG,
Sackin H,
and
Frindt G.
Regulation of Na channels by luminal Na in rat cortical collecting tubule.
J Physiol (Lond)
509:
151-162,
1998
21.
Reif, MC,
Troutman SL,
and
Schafer JA.
Sodium transport by rat cortical collecting tubule. Effects of vasopressin and desoxycorticosterone.
J Clin Invest
77:
1291-1298,
1986[ISI][Medline].
22.
Renard, S,
Voillet N,
Bassilana F,
Lazdunski M,
and
Barbry P.
Localization and regulation by steroids of the ,
and
subunits of the amiloride-sensitive Na+ channel in colon, lung and kidney.
Pflügers Arch
430:
299-307,
1995[ISI][Medline].
23.
Rossier, BC,
and
Palmer LG.
Mechanisms of aldosterone action on sodium and potassium transport.
In: The Kidney: Physiology and Pathophysiology, edited by Seldin DW,
and Giebisch G.. New York: Raven, 1992, p. 1373-1409.
24.
Schafer, JA,
Troutman SL,
and
Schlatter E.
Vasopressin and mineralocorticoid increase apical membrane driving force for K+ secretion in rat CCD.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F199-F210,
1990
25.
Schlatter, E,
and
Schafer JA.
Electrophysiological studies in principal cells of rat cortical collecting tubules.
Pflügers Arch
409:
81-92,
1987[ISI][Medline].
26.
Schwartz, GJ,
and
Burg MB.
Mineralocorticoid effects on cation transport by cortical collecting tubules in vitro.
Am J Physiol Renal Fluid Electrolyte Physiol
235:
F576-F585,
1978
27.
Stokes, JB.
Potassium secretion by cortical collecting tubule: relation to sodium reaborption, luminal sodium concentration and transepithelial voltage.
Am J Physiol Renal Fluid Electrolyte Physiol
241:
F395-F402,
1981
28.
Terris, JT,
Ecelbarger CA,
Nielsen S,
and
Knepper MA.
Long-term regulation of four renal aquaporins in rats.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F414-F422,
1996
29.
Tomita, K,
Pisano JJ,
and
Knepper MA.
Control of sodium and potassium transport in the cortical collecting tubule of the rat. Effects of bradykinin, vasopressin, and deoxycorticosterone.
J Clin Invest
76:
132-136,
1985[ISI][Medline].
30.
Velázquez, H,
Ellison DH,
and
Wright FS.
Chloride-dependent potassium secretion in early and late renal distal tubules.
Am J Physiol Renal Fluid Electrolyte Physiol
253:
F555-F562,
1987
31.
Verrey, F.
Early aldosterone action: toward filling the gap between transcription and transport.
Am J Physiol Renal Physiol
277:
F319-F327,
1999
32.
Will, PC,
Cortright RN,
DeLisle RC,
Douglas JG,
and
Hopfer U.
Regulation of amiloride-sensitive electrogenic sodium transport in the rat colon by steroid hormones.
Am J Physiol Gastrointest Liver Physiol
248:
G124-G132,
1985