Laboratory of Epithelial Transport, Division of Nephrology, Hypertension, and Transplantation, Department of Medicine, University of Florida, and Nephrology Section, Veterans Affairs Medical Center, Gainesville, Florida 32608-1197
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ABSTRACT |
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We studied the activation of
H+-K+-ATPase by CO2 in the renal
cortical collecting duct (CCD) of K-restricted animals. Exposure of
microperfused CCD to 10% CO2 increased net total
CO2 flux (Jt CO2) from
4.9 ± 2.1 to 14.7 ± 4 pmol · mm1
· min
1 (P < 0.05), and this effect was
blocked by luminal application of the
H+-K+-ATPase inhibitor Sch-28080. In the
presence of luminal Ba, a K channel blocker, exposure to
CO2 still stimulated
Jt CO2 from 6.0 ± 1.0 to
16.8 ± 2.8 pmol · mm
1 · min
1 (P < 0.01), but peritubular
application of Ba inhibited the stimulation. CO2
substantially increased 86Rb efflux (a K tracer
marker) from 93.1 ± 23.8 to 249 ± 60.2 nm/s (P < 0.05). These observations suggest that during K
restriction 1) the enhanced
H+-K+-ATPase-mediated acidification after
exposure to CO2 is dependent on a basolateral Ba-sensitive
mechanism, which is different from the response of rabbits fed a
normal-K diet, where activation of the
H+-K+-ATPase by exposure to CO2 is
dependent on an apical Ba-sensitive pathway; and 2) K/Rb
absorption via the apical H+-K+-ATPase exits
through a basolateral Ba-sensitive pathway. Together, these data are
consistent with the hypothesis of cooperation between H+-K+-ATPase-mediated acidification and K exit
pathways in the CCD that regulate K homeostasis.
hydrogen-potassium-adenosine 3',5'-triphosphatase; cortical collecting duct; acidification; Sch-28080
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INTRODUCTION |
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THE APICAL MEMBRANE of the collecting duct possesses an H+-K+-ATPase that is responsible for potassium (K) absorption in exchange for proton (H) secretion (9, 20). This enzyme appears to serve an important physiological role in the regulation of acid-base balance and potassium homeostasis (18). Changes in acid-base balance have a marked effect on potassium transport that is most notable in the distal nephron and collecting duct (11). Several studies have demonstrated that total CO2 flux (Jt CO2) is stimulated in the collecting duct when the ambient CO2 tension (PCO2) is increased (10, 12, 24). During respiratory acidosis induced by 10% CO2, the cortical collecting duct (CCD) from rabbits adapted to a normal-K diet (K repletion) exhibits enhanced luminal acidification (24). The acidification is in part due to a stimulation of H+-K+-ATPase activity in this segment and can be inhibited by luminal Sch-28080, a specific H+-K+-ATPase inhibitor. Under the same K-replete conditions, the activity of H+-K+- ATPase is also dependent on an apical barium (Ba)-sensitive pathway (24). The coupling of an apical H+-K+-ATPase and an apical Ba-sensitive mechanism (presumably a K channel) has been further supported by the observation that, in the presence of luminal Ba, stimulation by 10% CO2 does not increase either apical proton secretion or 86Rb efflux from lumen to bath (24).
To further address the regulatory mechanism of H+-K+-ATPase in the CCD, we examined the activation of the H+-K+-ATPase after exposure to 10% CO2 in K-restricted rabbits. The present studies are consistent with the hypothesis that an increase in peritubular PCO2 profoundly stimulates H+-K+-ATPase activity. In contrast to findings during K-repletion, this stimulation depends on a basolateral Ba-sensitive pathway, and stimulation of H+-K+-ATPase by 10% CO2 increases lumen-to-bath 86Rb efflux. Overall, these data add to our knowledge of the regulation of the H+-K+-ATPase function in the collecting duct in response to changes in potassium intake.
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MATERIALS AND METHODS |
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Animal preparations. Female New Zealand White rabbits were maintained on a low-K diet (0.25% K, TD87433, Teklad, Madison, WI) and allowed free access to tap water for at least 4 days before experimental use.
CCD isolation and microperfusion.
Standard in vitro microperfusion methods (2) as modified
in this laboratory were used (17). Briefly, rabbits were
decapitated, the left kidney was quickly removed, and 1- to 2-mm slices
were placed in a chilled petri dish containing the bath solution used in each protocol (Table 1) gassed with
5% CO2-95% O2. All of the dissection
solutions and bath solutions contain 5% vol/vol fetal calf serum.
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Chemicals and solutions. All chemicals were analytic grade or the highest available purity. [3H]inulin and 86Rb were obtained from New England Nuclear (Boston, MA). Sch-28080 (gift of Dr. James Kaninsky, Schering, Bloomfield, NJ) was dissolved in DMSO, and the final concentration of DMSO in perfusion solution did not exceed 0.1% (vol/vol).
The composition of the luminal perfusion and bath solutions for those experiments is listed in Table 1. The bath solutions were gassed with 5% CO2-95% O2 (pH = 7.4 ± 0.04) or 10% CO2-90% O2 (pH = 7.1 ± 0.03) for 60 min, respectively. The solution with 10% CO2 was regassed for 30 min just before use. The bath solutions were continuously exchanged at a rate of 0.64 ml/min. To facilitate comparison of the present results with the observations made from rabbits on a regular diet, the equilibration time between the 5 and 10% CO2 periods was at least 30 min. Our previous studies have shown that exposure to 10% CO2 for 30 min is sufficient to stimulate H+-K+-ATPase activity during K-replete conditions (24). All of the perfusates contained 50 µCi of [methoxy-3H]inulin exhaustively dialyzed according to the method of Schafer et al. (14) and were gassed with 5% CO2-95% O2. Effluent fluid was collected into a constant-volume pipette for measurement of volume flux (Jv), Jt CO2, and 86Rb efflux (KRb). The flow rate of the perfusate was maintained between 3.5 and 6.0 nl/min in the KRb and the Jt CO2 measurements.Jv measurement.
Jv was determined from timed collections of the
effluent fluid using the equation
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Jt CO2 measurement.
Luminal acidification rate was determined as
Jt CO2 (in pmol · mm1 · min
1) by microcalorimetry
and was calculated by the following formula
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86Rb efflux measurement.
K absorptive flux was assessed qualitatively as the 86Rb
lumen-to-bath efflux coefficient (KRb or
86Rb efflux in nm/s). 86Rb was selected because
stimulation of H+-K+-ATPase activity with Rb is
similar to that observed with K (3) and because these ions
are handled qualitatively similarly by the CCD (16).
86Rb efflux was determined by the disappearance of
86Rb from the perfusate according to the following equation
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Data analysis. All the data are expressed as means ± SE. Statistical analyses were performed by paired t-test or ANOVA for repeated measures as appropriate. Post hoc comparisons were made by the Ryan-Einot-Gabriel-Welch F-test. The null hypothesis was rejected at the 0.05 level of significance.
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RESULTS |
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Effect of 10% CO2 on
Jt CO2.
Figure 1A shows the
measurement of Jt CO2. Six
CCD tubules isolated from K-restricted rabbits were perfused with
solution A (Table 1) in both perfusate and bath (gassed with
5% CO2 as control).
Jt CO2 increased ~200% when 10%
CO2 was present in the bath solution (4.9 ± 2.1 pmol · mm1 · min
1 in the 5%
CO2 period; 14.7 ± 3.4 pmol · mm
1 · min
1 in the 10%
CO2 period; n = 6; P < 0.01). VT was not significantly affected
(2.3 ± 1.4 mV in 5% CO2 period and 1.5 ± 1.7 mV in 10% CO2 period; n = 6; Fig.
1B). The enhancement of
Jt CO2 with exposure to 10%
CO2 was similar to our previous observations from K-replete
rabbits (24), except that the magnitude of the Jt CO2 response in the present
studies is greater than that observed under the K-replete condition
(see Table 2).
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Effect of luminal Sch-28080 on Jt CO2.
To further examine the effect of 10% CO2 ascribed to the
H+-K+-ATPase, six tubules were perfused with
solution A symmetrically (with the addition of the
H+-K+-ATPase inhibitor Sch-28080 to the luminal
solution). Figure 2A shows
that 10 µM Sch-28080 completely abolished the stimulation of
Jt CO2 after exposure to 10%
CO2 (5.5 ± 1.0 pmol · mm1 · min
1 in 5% CO2
period; 4.3 ± 1.5 pmol · mm
1 · min
1 in 10% CO2 period; n = 6). The change in VT was not significantly different during these experiments (5% CO2 period,
1.7 ± 2.0 mV; 10% CO2 period,
1.9 ± 3.1 mV; n = 6; Fig. 2B). These data support the
assertion that stimulation of
Jt CO2 on exposure to 10%
CO2 is mediated by the
H+-K+- ATPase.
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Effect of luminal Ba on Jt CO2.
Because previous investigations in CCD from K-replete rabbits have
suggested that activation of the H+-K+-ATPase
on exposure to 10% CO2 is dependent on an apical
Ba-sensitive pathway (24), we examined whether a similar
response was observed in K-restricted rabbits. Five tubules were
perfused with solution A as bath and solution B
as perfusate with 2 mM Ba present throughout the entire experiment. As
shown in Fig. 3A, exposure to
10% CO2 markedly stimulated the
Jt CO2 even in the presence of 2 mM
luminal Ba (6.0 ± 1.0 pmol · mm1 · min
1 in the 5% CO2 period; 16.8 ± 2.8 pmol · mm
1 · min
1 in the 10%
CO2 period; n = 5; P < 0.01) without significantly affecting VT
(
13.1 ± 8.5 mV in 5% CO2 period and
11.8 ± 7.3 mV in 10% CO2 period; Fig. 3B). The present
data also show a tendency for VT in the presence
of luminal Ba to be more negative than under similar condition but
without luminal Ba during the 5% CO2 period (
13.1 ± 8.5 vs. 2.3 ± 1.4 mV; P = 0.08, not
significant by unpaired comparison). This could be due to an inhibitory
effect on apical K conductances. The same concentration of luminal Ba has been shown to make VT during the 5%
CO2 period become more negative than that without luminal
Ba and to inhibit the stimulation of
Jt CO2 by 10% CO2
under K-replete conditions (24).
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Effect of bath Ba on Jt CO2.
The previous observations raise the possibility that activation of the
H+-K+- ATPase by 10% CO2 during
K restriction may be dependent on a basolateral Ba-sensitive pathway,
because the apical Ba-sensitive pathway seems not be involved in this
condition. To test this hypothesis, six tubules were perfused with
solution B containing 2 mM Ba in the bath and solution
C as perfusate. As shown in Fig. 4A, peritubular application of
2 mM Ba fully inhibited the stimulation of
Jt CO2 after exposure to 10%
CO2 (3.4 ± 1.2 pmol · mm1
· min
1 in 5% CO2 period; 1.8 ± 1.0 pmol · mm
1 · min
1 in 10%
CO2 period; n = 7).
VT was not significantly altered during the
experiments (5% CO2 period, 3.5 ± 1.5 mV; 10%
CO2 period, 3.3 ± 1.2 mV; n = 7).
These data suggest that the effect of 10% CO2 on
acidification is dependent on a basolateral Ba-sensitive pathway.
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86Rb efflux response to 10% CO2 and effect of Sch-28080 on 86Rb efflux. Because 86Rb trace efflux is a qualitative marker of K efflux, we examined whether exposure to 10% CO2 increased KRb from lumen to bath and whether H+-K+-ATPase mediated the effect of 10% CO2 on KRb in CCD of K-restricted rabbits. The tubules were perfused with symmetrical solution A containing either vehicle, 0.1% DMSO, or 10 µM Sch-28080 in the luminal perfusate.
As shown in Fig. 5A, 10% CO2 substantially increased KRb from 93.1 ± 23.8 to 249 ± 60.2 nm/s (n = 7; P < 0.05). The stimulation of KRb by 10% CO2 is consistent with an increase of K efflux from lumen to bath.
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Effect of bath Ba on 86Rb efflux.
The purpose of the next experiment was to examine whether a basolateral
Ba-sensitive pathway of CCD mediates the stimulation of
KRb after exposure to 10% CO2 in
K-restricted rabbits. In six experiments the CCD was perfused with
solution B containing 3 mM Ba as the bath and solution
C as the perfusate. Figure
7A shows that Ba totally
abolished the stimulation of KRb by 10%
CO2 (73.0 ± 8.2 nm/s in 5% CO2 period;
70.9 ± 8.3 nm/s in 5% CO2 period; n = 6). The present observations indicate that the effect of 10% CO2 on KRb by the CCD from
K-restricted rabbits is different from that observed in the CCD of
rabbits exposed to a normal diet (24) and is in agreement
with the data on Jt CO2 presented
previously (see Figs. 1 and 4). Thus a Ba-sensitive pathway appears to
be present in the basolateral membrane of the rabbit CCD during K restriction, and this pathway mediates the stimulatory effect of 10%
CO2 on KRb. The
VT became slightly less lumen-negative, but the
effect was not significant (from 2.2 ± 3.0 mV in 5%
CO2 period to
0.0 ± 1.7 mV in 10% CO2
period) (n = 6; P = not significant; Fig. 7B).
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DISCUSSION |
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H+-K+-ATPase appears to be primarily responsible for enhanced luminal acidification after exposure to 10% CO2 under normal conditions (24). Apical K absorption by H+-K+-ATPase recycles at the luminal membrane, but during K restriction this enzyme is responsible for both H secretion and K absorption, as demonstrated by our previous (19, 22, 23) and present studies.
Our previous studies (24) from K-replete rabbits have shown that exposure to 10% CO2 profoundly enhanced total CO2 flux of the CCD, and this enhancement was totally blocked by luminal application of either Sch-28080 or Ba. In contrast, exposure to 10% CO2 failed to stimulate Rb efflux by the CCD. These data suggest that stimulation of total CO2 flux on exposure to 10% CO2 is dependent on both the apical H+-K+-ATPase and the apical Ba-sensitive pathway, which leads to our proposal that apical K absorption via the H+-K+-ATPase recycles at the apical membrane via a Ba-sensitive exit mechanism (24). However, the results are quite different in the present studies performed in this segment from rabbits maintained on a K-restricted diet.
First, the magnitude of stimulation of total CO2 flux by
exposure to 10% CO2 under K-restricted conditions is
significantly greater than that observed under normal conditions
(9.8 ± 1.7 vs. 3.5 ± 0.6 pmol · mm1 · min
1) (see Table 2). This
observation is consistent with the enzymatic data that demonstrate
increased K-dependent ATP hydrolysis in the permeablized CCD after
exposure to a K-deprived diet (3, 4).
Second, although exposure to 10% CO2 dramatically augmented the Sch-28080-inhibitable total CO2 flux (Figs. 1A and 2A), this effect does not rely on the apical Ba-sensitive pathway because luminal Ba failed to alter the response of the CCD to 10% CO2 (Fig. 3A). On the other hand, this Jt CO2does depend on the basolateral Ba-sensitive mechanism, because peritubular Ba completely abolished the stimulation of total CO2 after exposure to 10% CO2 (Fig. 4A).
Third, exposure to 10% CO2 substantially increased the Sch-28080-sensitive 86Rb efflux (Figs. 5A and 6A), and this effect was completely inhibited by peritubular application of Ba (Fig. 7A). However, our previous investigations of K-restricted animals showed that in the presence of luminal Ba, Sch-28080-sensitive 86Rb efflux could still be enhanced (23). These data are consistent with a model in which Rb/K that enters the cell via the apical H+-K+-ATPase under 10% CO2 stimulation exits the cell via a basolateral Ba-sensitive pathway.
Fourth, in our present study, VT did not significantly change from the 5% CO2 period to the 10% CO2 period in the K-restricted rabbits (Fig. 1B). In contrast, CCD in the normal-K-diet rabbits became significantly less lumen negative in the 10% CO2 period (see Table 2). If the differences in K-restricted rabbits and in normal-K-diet rabbits suggest a K-conserving role for the former and a K-recycling role for the later, we should see a more negative VT during 10% CO2 stimulation in the K-restricted rabbits. It is possible that a parallel Cl current was also activated in the basolateral membrane during the 10% CO2 period, which could mitigate the change in VT. The VT in the 5% CO2 period in the presence of luminal Ba was more negative than that without luminal Ba (see Fig. 3B vs. 1B). In our previous experiments with animals in K repletion, we observed a similar effect of luminal Ba on VT (Table 2), although the magnitude of the effect appeared greater, consistent with a greater apical K conductance in K-replete animals.
In the experiments that examined the effect of 10% CO2 on 86Rb efflux, VT became more lumen positive (or less negative) regardless of the absence or presence of luminal Sch-28080 (see Figs. 5B and 6B). The exact reason for VT changes in these experiments is not known. This may reflect differences in the electrogenic Na absorption among the tubules and the sensitivity of this process to 10% CO2, but the present study does not separate these effects. The theoretical estimation of the effect of the VT change on 86Rb efflux is <10% of the total measured enhancement (Fig. 5C). In addition, Sch-28080 completely inhibited the effect of 10% CO2 on KRb (Fig. 6A), which also provides evidence that the H+-K+-ATPase, not the change in voltage, mediates enhancement of 86Rb efflux on exposure to 10% CO2.
Our previous investigations of K-restricted animals showed that removal of luminal Na could enhance 86Rb efflux, and the enhancement was inhibited by the luminal application of the H+-K+-ATPase inhibitor Sch-28080, but not by luminal Ba (23). This indicates that luminal Ba does not directly inhibit the action of the H+-K+-ATPase. Our previous studies from K-replete animals showed that 86Rb efflux was actually decreased in response to 10% CO2 and this decrease was abolished when apical Ba was present (24). Our present data from K-restricted animals suggest that under 10% CO2, a Ba-sensitive K exit pathway is present in the basolateral membrane of the CCD, and this pathway participates in Rb/K absorption. Thus the basolateral K exit mechanisms appear to play a critical role in differentiating the response to 10% CO2 under K-restricted conditions from that observed under K-replete conditions.
Several studies have shown that the basolateral membrane of rat CCD has Ba-sensitive K conductances (6, 15). Similar Ba-sensitive K conductances were also revealed in the basolateral membrane of rabbit CCD (8, 13). It is possible that blockade of K channels increases the intracellular K activity, which secondarily inhibits the H+-K+-ATPase and thus Jt CO2 (see Fig. 4A) (7, 21). However, Ba may not only affect K channels. For example, Ba also inhibits a K-Cl cotransporter as demonstrated by Greger and Schlatter (5) in the thick ascending limb of Henle's loop. Therefore, future investigation is needed to understand the exact mechanisms of basolateral K exit under stimulation of 10% CO2.
Although the present study has focused on the H+-K+-ATPase stimulation by 10% CO2, our data show that basolateral Ba had a tendency to inhibit Rb efflux, but not significantly with 5% CO2 (unpaired comparison of Figs. 5A and 7A). Because we have not formally examined the quantitative contribution of this basolateral Ba-sensitive mechanism to transepithelial 86Rb efflux, we cannot exclude a significant effect in paired studies of Ba on KRb with 5% CO2.
Our data suggest that apical K absorption via an apical
H+-K+-ATPase may exit the cell through either
an apical K secretory mechanism or a basolateral K- absorptive
mechanism, depending on total body K homeostasis. We propose a cell
model showing the coupling of an apical membrane
H+-K+-ATPase and a K exit during cellular
acidification in K-replete and K-restricted conditions (Fig.
8). This model is based primarily on the
differences observed from previous K-replete (24) and present K-restricted rabbits with respect to exposure to 10%
CO2. Neither the present study nor evidence in the
literature allows unambiguous distinction of the cell types involved in
the response to 10% CO2. Some recent data suggest that
H+-K+-ATPase 1-subunit is
expressed in principal cells (
1 mRNA) (1), although antibody studies localize the
H+-K+-ATPase
1-subunit to the
apical membrane of intercalated cells (19). The
possibility that both cell types respond cannot be excluded.
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In summary, we have shown that during K restriction exposure to 10% CO2 substantially increased the Sch-28080-sensitive JtCO2 even in the presence of luminal Ba and this effect was abolished by peritubular application of Ba. In addition, exposure to 10% CO2 profoundly stimulated 86Rb efflux by the CCD from the K-restricted rabbit, and this stimulation was inhibited not only by luminal application of Sch-28080 but also by peritubular application of Ba. These studies demonstrate that enhancement of H+-K+-ATPase-mediated acidification by 10% CO2 during K restriction is not dependent on an apical Ba-sensitive pathway but rather dependent on a basolateral Ba-sensitive pathway.
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ACKNOWLEDGEMENTS |
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The authors thank Wei L. Ueberschaer for technical assistance in some experiments reported in this manuscript.
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FOOTNOTES |
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These studies were supported by funds from the Medical Research Service of the Department of Veterans Affairs and by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-49750.
Present address of X. Zhou: Dept. of Medicine, Uniformed Services Univ. of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799.
Address for reprint requests and other correspondence: C. S. Wingo, Nephrology and Hypertension (111G), Veterans Affairs Medical Center, Gainesville, FL 32608-1197.
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. §1734 solely to indicate this fact.
Received 8 June 1999; accepted in final form 29 February 2000.
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REFERENCES |
---|
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---|
1.
Ahn, KY,
and
Kone BC.
Expression and cellular localization of mRNA encoding the "gastric" isoform of the H+-K+-ATPase in rat kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
268:
F99-F109,
1995
2.
Burg, MB,
Grantham JJ,
Abramow M,
and
Orloff J.
Preparation and study of fragments of single rabbit nephrons.
Am J Physiol
210:
1293-1298,
1966[ISI][Medline].
3.
Cheval, L,
Barlet-Bas C,
Khadouri C,
Feraille E,
Marsy S,
and
Doucet A.
K+-ATPase-mediated Rb+ transport in rat collecting tubule: modulation during K+ deprivation.
Am J Physiol Renal Fluid Electrolyte Physiol
260:
F800-F805,
1991
4.
Dafnis, E,
Spohn M,
Lonis B,
Kurtzman NA,
and
Sabatini S.
Vanadate causes hypokalemic distal renal tubular acidosis.
Am J Physiol Renal Fluid Electrolyte Physiol
262:
F439-F444,
1992.
5.
Greger, R,
and
Schlatter E.
Properties of the basolateral membrane of the cortical thick ascending limb of Henle's loop of rabbit kidney.
Pflügers Arch
396:
325-334,
1983[ISI][Medline].
6.
Hirsch, J,
and
Schlatter E.
K+ channels in the basolateral membrane of rat cortical collecting duct are regulated by a cGMP-dependent protein kinase.
Pflügers Arch
429:
338-344,
1995[ISI][Medline].
7.
Koelz, HR,
Sachs G,
and
Berglindh T.
Cation effects on acid secretion in rabbit gastric glands.
Am J Physiol Gastrointest Liver Physiol
241:
G431-G432,
1981
8.
Koeppen, B,
and
Giebisch G.
Cellular electrophysiology of potassium transport in the mammalian cortical collecting tubule.
Pflügers Arch
405, Suppl1:
S143-S146,
1985[ISI][Medline].
9.
Kone, BC.
Renal H,K-ATPase: structure, function and regulation.
Miner Electrolyte Metab
22:
349-365,
1996[ISI][Medline].
10.
Laski, ME,
and
Kurtzman NA.
Collecting tubule adaptation to respiratory acidosis induced in vivo.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F15-F20,
1990
11.
Malnic, G,
DeMello Aires M,
and
Giebisch G.
Potassium transport across renal distal tubules during acid-base disturbances.
Am J Physiol
221:
1192-1208,
1971[ISI][Medline].
12.
McKinney, TD,
and
Davidson KK.
Effects of respiratory acidosis on HCO3 transport by rabbit collecting tubules.
Am J Physiol Renal Fluid Electrolyte Physiol
255:
F656-F665,
1988
13.
Sansom, SC,
and
O'Neil RG.
Effects of mineralocorticoids on transport properties of cortical collecting duct basolateral membrane.
Am J Physiol Renal Fluid Electrolyte Physiol
250:
F743-F757,
1986.
14.
Schafer, JA,
Troutman SL,
and
Andreoli TE.
Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules.
J Gen Physiol
64:
582-607,
1974
15.
Wang, WH,
Mcnicholas CM,
Segal AS,
and
Giebisch G.
A novel approach allows identification of K channels in the lateral membrane of rat CCD.
Am J Physiol Renal Fluid Electrolyte Physiol
266:
F813-F822,
1994
16.
Warden, DH,
Hayashi M,
Schuster VL,
and
Stokes JB.
K+ and Rb + transport by the rabbit CCD: Rb+ reduces K+ conductance and Na+ transport.
Am J Physiol Renal Fluid Electrolyte Physiol
257:
F43-F52,
1989
17.
Wingo, CS.
Active proton secretion and potassium absorption in the rabbit outer medullary collecting ductfunctional evidence for proton-potassium activated adenosine triphosphatase.
J Clin Invest
84:
361-365,
1989[ISI][Medline].
18.
Wingo, CS,
and
Cain BD.
The renal H-K-ATPase: physiological significance and role in potassium homeostasis.
Annu Rev Physiol
55:
323-347,
1993[ISI][Medline].
19.
Wingo, CS,
Madsen KM,
Smolka A,
and
Tisher CC.
H-K-ATPase immunoreactivity in cortical and outer medullary collecting duct.
Kidney Int
38:
985-990,
1990[ISI][Medline].
20.
Wingo, CS,
and
Smolka AJ.
Function and structure of H,K-ATPase in the kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
269:
F1-F16,
1995
21.
Zhou, X,
and
Wingo CS.
H-K-ATPase enhancement of Rb efflux by cortical collecting duct.
Am J Physiol Renal Fluid Electrolyte Physiol
263:
F43-F48,
1992
22.
Zhou, X,
and
Wingo CS.
Mechanisms for enhancement of Rb efflux by 10% CO2 in cortical collecting duct (CCD) (Abstract).
Clin Res
40:
179A,
1992.
23.
Zhou, X,
and
Wingo CS.
Mechanisms of rubidium permeation by rabbit cortical collecting duct during potassium restriction.
Am J Physiol Renal Fluid Electrolyte Physiol
263:
F1134-F1141,
1992
24.
Zhou, X,
and
Wingo CS.
Stimulation of total CO2 flux by 10% CO2 in rabbit CCD: role of an apical Sch-28080- and Ba-sensitive mechanism.
Am J Physiol Renal Fluid Electrolyte Physiol
267:
F114-F120,
1994