Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, Texas 77225
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
86Rb fluxes through ATP-regulated K+ (KATP) channels in membrane vesicles derived from basolateral membranes of Necturus small intestinal epithelial cells as well as the activity of single KATP channels reconstituted into planar phospholipid bilayers are inhibited by the presence of ADP plus phosphoenolpyruvate in the solution bathing the inner surface of these channels. This inhibition can be prevented by pretreatment of the membranes with 2,3-butanedione, an irreversible inhibitor of pyruvate kinase (PK) and reversed by the addition of 2-deoxyglucose plus hexokinase. The results of additional studies indicate that PK activity appears to be tightly associated with this membrane fraction. These results, together with considerations of the possible ratio of Na+-K+ pumps to KATP channels in the basolateral membrane, raise the possibility that "cross talk" between those channels and pumps (i.e., the "pump-leak parallelism") may be mediated by local, functionally compartmentalized ATP-to-ADP ratios that differ from those in the bulk cytoplasm.
adenosine 5'-triphosphate-regulated potassium channels; small intestine; epithelial transport; glycolysis; cross talk; pyruvate kinase
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
ATP-REGULATED K+ (KATP) channels have been identified in the plasma membranes of a wide variety of cells, where they appear to couple membrane properties to cell metabolic state. Although these channels comprise a large, diverse family exhibiting many qualitative and quantitative differences, they share the common property of being inhibited by ATP as well as by nonhydrolyzable analogs of that nucleotide (2). We (8) and others (4, 5, 13, 21, 22, 32, 33) have identified such channels in the basolateral membranes of several Na+-absorbing epithelial cells and have suggested that they may be responsible for, or contribute to, the parallelism between the Na+-K+ pump activity and the K+ conductance of those barriers observed to date in all Na+-absorbing epithelial cells; thus an increase in pump activity would lead to a decrease in local ATP concentration and a consequent increase in channel activity, and vice versa. The importance of this pump-leak parallelism has been discussed elsewhere (27, 28).
The present studies were designed to examine the possibility that the KATP channel in the basolateral membrane of Necturus maculosa enterocytes can be affected by ATP produced locally from glycolytic substrates. They were prompted by reports that ATP derived from the action of membrane-associated glycolytic enzymes serves, preferentially, to regulate the KATP channel in cardiac muscle membranes (34) and to fuel the Na+-K+ pump and the Ca2+ pump in some cells (3, 11, 20, 23, 25). Our results demonstrate the presence of membrane-associated pyruvate kinase (PK) activity and support the notion that ATP may be "functionally compartmentalized" at the inner surface of the basolateral membrane.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Studies were initially carried out to assess the effects of glycolytic substrates on 86Rb+ uptake by basolateral membrane vesicles and, subsequently, to evaluate the effects of these substrates on the activity of single KATP channels in membrane fragments reconstituted into planar phospholipid bilayers.
Membrane isolation. The methods for isolating a basolateral membrane fraction from Necturus enterocytes have been described in detail (6). Briefly, a membrane fraction enriched in Na+-K+-ATPase activity was isolated from mucosal scrapings of Necturus small intestine by differential centrifugation without the use of enzymes. The method results in a >20-fold enrichment of Na+-K+-ATPase activity over that in the crude homogenate, with minimal contamination by enzyme markers for membranes other than the basolateral membranes. The membranes are frozen, stored in liquid N2, and thawed immediately before use.
Studies on membrane vesicles. KATP channel activity was assayed using 86Rb+ as a tracer for K+ essentially as described by Garty et al. (10). Briefly, a freeze-thaw procedure was used to load vesicles with K2SO4, and the extravesicular K+ was then removed by passing the suspension through a cation exchange column. If the membrane possesses a K+ conductance, the intravesicular compartment will become markedly electrically negative with respect to the extravesicular compartment, thus providing a large electrical driving force for the accumulation of 86Rb+. As discussed by Garty et al. (10), under these conditions, the intravesicular compartment becomes a large "sink" for the tracer, thus obviating the need for rapid sampling techniques to estimate initial uptake rates of tracer. Furthermore, under these conditions, because of the voltage-gating properties of this channel (6), the open probability (Po) for channels whose inner mouths are oriented toward the intravesicular space will be close to unity, whereas the Po of those channels whose inner mouths face the extravesicular compartment will be close to zero; i.e., the intravesicular space will correspond to the intracellular compartment, and only outside-out vesicles will be active. After passage through the column, 86Rb+ was added to the suspension and aliquots were removed at various times and passed through a second ion exchange column to remove all extravesicular 86Rb+.
Specifically, columns were prepared from DOWEX 50W-X-8 (Tris form), poured into glass Pasteur pipettes, and pretreated with three drops of 30% BSA. The columns were washed with 4 ml of 300 mM mannitol-10 mM Tris-HEPES (pH 7.6). Vesicles were loaded by addition of 200 µl of suspension (containing 500 µg protein) to 40 µl of 0.5 M K2SO4, 5 mM MgCl2, and 10 mM K-HEPES (pH 7.0) and other reagents as indicated. The mixture was then frozen in liquid N2. After thawing, 200 µl of the suspension was pipetted onto the DOWEX column and eluted with 2 ml of 300 mM mannitol-10 mM Tris-HEPES (pH 7.0) under mild vacuum. Immediately after the vesicles were collected, a 10-µl aliquot of 86Rb+ (0.4 µCi) was added to initiate uptake. At timed intervals, starting immediately after the addition of tracer, 200-µl aliquots were withdrawn and placed on a second DOWEX column to remove all external tracer. The vesicles were eluted from the column with 2 ml of the mannitol buffer directly into scintillation vials and assayed for 86Rb+ content. Intravesicular 86Rb+ is expressed as the percent of total radioactivity in a 200-µl aliquot of reaction mixture.Studies of single-channel activities.
Planar phospholipid bilayers were formed by painting a mixture of
phosphatidylethanolamine and phosphatidylserine (50:50) dissolved in
decane (25 mg/ml) over a 300-µm aperture in a Delrin cup inserted
into a cut-away polyvinyl chloride block as described by Alvarez (1).
Channels were incorporated into the bilayer by extruding a small
aliquot of a freshly thawed suspension directly onto the bilayer,
employing a micropipette. The cup or
cis compartment initially contained 3 ml of 150 mM KCl plus 1 mM MgCl2,
and the trans compartment initially
contained 3 ml of 5 mM KCl plus 1 mM
MgCl2; both solutions were
buffered with 10 mM HEPES (Tris salt) to pH 7.0. The membrane was
clamped at a membrane potential (Vm) of
40 mV so that, as noted previously, the active channels would be
oriented such that the cis compartment
corresponds to the "intracellular solution" and the
trans compartment corresponds to the
"serosal solution." At the conclusion of every experiment, the
two solutions were withdrawn and their
K+ concentrations were determined
using flame photometry; K+
activities were calculated using the activity coefficients published by
Robinson and Stokes (26).
Enzyme assays.
The
Na+-K+-ATPase
activity was assayed spectrophotometrically using a regenerating
coupled NADH-linked reaction as described elsewhere (9). For the
determination of the endogenous activities of PK and lactic
dehydrogenase, an aliquot of membranes was added to a
reaction mixture that contained (in mM) 120 NaCl, 20 KCl, 20 Tris
(titrated to pH 7.4 with HCl), 3 ATP, 3 phosphoenolpyruvate (PEP), and 6 MgCl2, with 1 mg/ml
BSA. The oxidation of NADH was followed spectrophotometrically by
recording the optical density at 340 nm. The extinction coefficient
used for calculating the enzyme activities was 6.22 cm · ml · µmol1.
The activity of PK alone was determined by the inclusion of 10 µg/ml
lactic dehydrogenase to make PK activity rate limiting. The activity of
lactic dehydrogenase was determined in a parallel assay in which PK was
added to the reaction at 10 µg/ml, thereby leaving lactic
dehydrogenase rate limiting. Adenylate kinase was assayed as described
by Sottocasa et al. (30). Protein was determined by the method of Lowry
et al. (18), using BSA as a standard.
Reagents.
Valinomycin was purchased from Calbiochem (La Jolla, CA). Phospholipids
were purchased from Avanti Polar Lipids (Birmingham, AL). Ouabain, PK
(type II from rabbit muscle), lactic dehydrogenase (type II from rabbit
muscle), NADH, ATP, ADP, adenosine
5'-O-(3-thiotriphosphate) (ATPS), PEP, and 2,3-butanedione were all obtained from Sigma Chemical (St. Louis, MO). All other reagents were of the highest purity available.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The time courses of
86Rb+
uptake into control vesicles preloaded with 100 mM
K2SO4
plus 1 mM MgCl2 and into vesicles
that, in addition, contained 1 mM ATPS are illustrated in Fig.
1. Clearly, this
nonhydrolyzable analog of ATP completely abolishes uptake. Treatment of
the vesicles that were preloaded with ATP
S with the
K+ ionophore valinomycin (1 µg/ml) restored 86Rb uptake,
indicating that the preloading procedure did not disrupt the
vesicles.1
Thus, in the absence of valinomycin, the only appreciable
K+ conductance in these vesicles
is the KATP channel; the membranes are otherwise "tight" to that cation. In addition, these findings indicate that the measurements reflect true uptake and not simply binding to the membranes and that these measurements are not
significantly affected by contamination with extravesicular fluid.
|
As shown in Fig. 2, preloading the vesicles
with 1 mM ADP resulted in an inhibition of
86Rb+
uptake that could be prevented by the inclusion of 2-deoxyglucose (10 mM) and hexokinase (2.7 U/ml) in the preloading solution. These results
suggested that ADP was being converted to ATP within the vesicle,
probably through the action of adenylate kinase. As shown in Table
1, adenylate kinase activity could be
detected in the basolateral membrane fraction, but after freezing and
thawing of the vesicles there was a 70% reduction in
activity to a barely detectable level of 0.004 µmol · mg1 · min
1.
Thus adenylate kinase appears to be largely a soluble, cytoplasmic enzyme, but it is possible that residual activity could account for the
findings shown in Fig. 2.
|
|
To examine this matter further, the vesicles were preloaded with 5 mM PEP plus 1 mM ADP. To optimize ATP production, 5 mM NADH was also included in the loading solution to drive the conversion of pyruvate to lactate. As shown in Fig. 3, this resulted in complete inhibition of channel activity, which could be largely reversed by pretreatment with 2,3-butanedione (50 mM), an irreversible inhibitor of PK (14), in the preloading solution; preincubation of the vesicles with 2,3-butanedione did not, by itself, affect 86Rb+ uptake.
|
Finally, direct measurements of the activities of PK and lactic dehydrogenase demonstrated the presence of both enzymes in the vesicle preparation. As shown in Table 2, although the specific activity of neither enzyme in the basolateral membrane fraction exceeds that of the total homogenate, the overall sequence from PEP to lactate, which is necessary for optimal ATP generation, showed a four- to fivefold increase in specific activity. After freezing and thawing in a dilute solution, 52% of the PK activity, 27% of the lactic dehydrogenase activity, and 37% of the overall PEP-to-lactate activity were recovered in the pelleted membrane fraction, suggesting that the enzymes may be membrane bound or compartmentalized within the vesicles.
|
These results are consistent with the interpretation that the KATP channel can be inhibited by intravesicular ATP generated from PEP plus ADP through the action of PK. However, it is not entirely clear from these results whether these enzymes are truly membrane associated or whether they are cytoplasmic contaminants of the vesicle preparation. Furthermore, if this line of argument is correct, this system does not permit distinction between an increase in bulk, intravesicular ATP and ATP contained within a restricted domain adjacent to the inner surface of the membrane; we have previously shown (8) that the channel is inactivated in the presence of 0.5-1 mM ATP and that activity can be partially restored by high concentrations of ADP (5-10 mM). In an attempt to resolve these issues, a series of experiments was performed to explore the effects of glycolytic substrates on the activity of single KATP channels reconstituted into planar phospholipid bilayers.
As shown in Fig. 4, single-channel activity was not affected by exposure to 1 mM ADP in the cis compartment for at least 3 min. But, the subsequent addition of 5 mM PEP to the cis solution resulted in a significant reduction in single-channel activity within 1 min and complete inhibition by 3-5 min. Identical results were obtained by reversing the sequence of addition of these reagents. These findings suggest that the inhibition of 86Rb+ uptake observed when ADP was included in the vesicle (Fig. 2) was probably the result of residual adenylate kinase activity in the crude vesicle preparation that was lost when the vesicles were incorporated into the phospholipid bilayer. In nine experiments, the combined presence of cis PEP and ADP either completely abolished channel activity or resulted in a substate with markedly reduced single-channel conductance. Treatment of vesicles with 2,3-butanedione, before reconstitution into the phospholipid bilayer, prevented the inhibitory effects of cis PEP plus ADP (n = 6).
|
Furthermore, as illustrated in Fig. 5, addition of 10 mM 2-deoxyglucose plus hexokinase (2.7 U; n = 9) restored channel activity to a full conductance state (n = 4), to a subconductance state (n = 3), or to a flickering state (n = 2). Addition of 2-deoxyglucose alone and addition of hexokinase alone to the cis compartment were ineffective in restoring channel activity. As illustrated in Fig. 5B, stirring alone after channel inhibition by PEP plus ADP did not restore channel activity. However, the addition of 2-deoxyglucose plus hexokinase reversed the inhibition. These findings are consistent with the notion that these reactions take place in a domain that is resistant to stirring but is accessible to large solutes by diffusion.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
It is well established that there is a close parallelism between the Na+-K+ pump activities and the K+ conductances of the basolateral membranes of all Na+-absorbing epithelial cells studied to date, such that an increase in pump activity is accompanied, very rapidly and precisely, by a parallel increase in K+ conductance, and vice versa (4, 27, 28). This pump-leak parallelism serves to preserve the electrical driving force for electrogenic or rheogenic Na+ entry processes across the apical membrane, as well as preserving cell K+ content and cell volume in the face of large, and often rapid, changes in the rate of transcellular Na+ absorption. The discovery of K+ channels that can be inhibited by ATP, first in cardiac muscle membranes (24) and later in a wide variety of cells (2), raised the attractive possibility that ATP or the ATP-to-ADP ratio may serve as the signal that orchestrates Na+ pump and K+ leak activities (28), and the finding of KATP channels in the basolateral membranes of rabbit (13, 32) and Ambystoma (21, 22) proximal tubule, frog skin (33), and Necturus small intestinal (8) epithelial cells supports that notion at least for these Na+-absorbing epithelial cells.
The present results indicate that the activity of KATP channels in the basolateral membranes of Necturus enterocytes may be influenced by ATP formed in the vicinity of these channels through the action of PK that is associated with this membrane. Similar findings have been reported by Weiss and Lamb (34) for KATP channels in cardiac myocyte membranes studied with the patch-clamp technique. Furthermore, our finding that the inhibition of single channels reconstituted into planar phospholipid bilayers by PEP plus ADP could not be readily reversed by stirring the cis solution suggests that this local region may not simply be an unstirred layer adjacent to the bilayer, albeit accessible to relatively large solutes by diffusion. Lederer et al. (17) postulated the presence of a "fuzzy space," defined as a "functionally restricted intracellular space," to explain the interactions among plasma membrane Na+ channels, Na+-Ca2+ antiporters, and Ca2+ release channels in the underlying sarcoplasmic reticulum of heart muscle; evidence consistent with that notion has been more recently reported by Trafford et al. (31). Semb and Sejersted (29) have also invoked the notion of a "micro-environment close to the membrane where diffusion is slower than in the rest of the cytoplasm" to explain the regulation of the Na+-K+ pump by intracellular Na+ activity in heart and skeletal muscle. With respect to the present findings, it may be of interest that glycolytic enzymes are known to be avidly bound to F-actin (cf. Ref. 14) and that actin is concentrated just below most plasma membranes (so-called "cortical-actin"; cf. Ref. 19). Actin is tightly bound to our basolateral membrane vesicles and appears to be present at the inner face of the vesicles following reconstitution into planar bilayers (unpublished observations). Thus it is quite possible that this cortical actin meshwork forms a restricted submembrane domain that permits functional coupling of PK activity with KATP channels.
Functionally compartmentalized ATP derived from glycolysis, near the plasma membrane, has also been postulated to preferentially fuel the Na+-K+ pump in human red blood cells (23, 25), Madin-Darby canine kidney cells (20), and Rous-transformed hamster cells and Ehrlich ascites tumor cells (3). Hardin et al. (12) have arrived at a similar conclusion for the Ca2+ pump in smooth muscle plasma membrane. The possibility that the ATP pool that is utilized by the pumps and that influences KATP channel activity is also localized takes on added significance from the fact that, under steady-state conditions, the basolateral membrane possesses many more functional pumps (which are consumers of ATP and producers of ADP) than channels.2 Thus these considerations, together with the finding of local glycolytic production of ATP, raise the admittedly speculative possibility that the ATP and ADP activities in the environment around the inner face of a channel may differ from their bulk cytoplasmic activities and that it is this local environment that influences KATP channel activity.
![]() |
ACKNOWLEDGEMENTS |
---|
This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-45251 (to S. G. Schultz) and DK-38518 (to W. P. Dubinsky).
![]() |
FOOTNOTES |
---|
1
The close correspondence between uptake via the
channel and uptake in the presence of valinomycin may not be
coincidental. From the data reported by Läuger (16), the
conductance of a phospholipid membrane in the presence of valinomycin
at a concentration of 1 µg/ml and a mean concentration of
K+ of ~50 mM should be
~103
S/cm2. The diameters of our
vesicles range between 200 and 500 nm, so that the valinomycin-induced
conductance should be ~40-75 pS/vesicle. The conductance of the
channel under these conditions is 100-150 pS. Thus our findings
would be consistent with the notion that, on the average, each vesicle
possesses one channel and the orientation of the channel in 50% of the
vesicles renders it inactive.
2
Under "optimal conditions," the turnover
number of the
Na+-K+
pump is estimated to be between 200 and 500 s1 (7); thus, every 1 s, an
active pump consumes 200-500 ATP molecules and pumps
400-1,000 K+ into the cell in
exchange for 600-1,500 Na+
pumped out of the cell. Now, the current through a single
K+ channel is given by
IK = Pogc[Vm
EK
], where gc
is the single-channel conductance,
Vm is the
membrane potential,
EK is the Nernst
equilibrium potential for K+, and
Po is the open
probability or the fraction of time the channel is in the fully open,
conducting configuration. If it is assumed that the ratio of
intracellular to extracellular K+
activities is ~20 (i.e., 100:5 mM) and that
Vm is
approximately
40 mV (27), then
EK is
approximately
80 mV and the driving force for
K+ diffusion from the cell is
~40 mV. Now, under these conditions, gc for our
KATP channel is ~150 pS. Thus,
when the channel is open,
IK is ~6 pA,
which is the equivalent of ~40 × 106
K+/s. It follows that, when
Po = 1, the
amount of K+ that diffuses out of
the cell through a single channel is equivalent to the amount that is
pumped into the cell by roughly 30,000-75,000 active pumps. Or,
stated in other words, just one K+
channel would suffice to recycle across the basolateral membrane the
amount of K+ pumped into the cell
by ~104 pumps. Even when
Po = 0.001, the
number of active pumps must exceed the number of channels by at least
one order of magnitude.
Address for reprint requests: S. G. Schultz, Dept. of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, PO Box 20708, Houston, TX 77225.
Received 30 October 1997; accepted in final form 27 August 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Alvarez, O.
How to set up a bilayer system.
In: Ion Channel Reconstitution, edited by C. Miller. New York: Plenum, 1986, p. 115-130.
2.
Ashcroft, S. J. H.,
and
F. M. Ashcroft.
Properties and functions of ATP-sensitive K-channels.
Cell. Signal.
2:
197-214,
1990[Medline].
3.
Balaban, R. S.,
and
J. P. Bader.
Studies on the relationship between glycolysis and (Na+-K+)-ATPase in cultured cells.
Biochim. Biophys. Acta
804:
419-426,
1984[Medline].
4.
Beck, J. S.,
R. Laprade,
and
J.-Y. Lapointe.
Coupling between transepithelial Na transport and basolateral K conductance in renal proximal tubule.
Am. J. Physiol.
266 (Renal Fluid Electrolyte Physiol. 35):
F517-F527,
1994
5.
Broillet, M.-C.,
and
J.-D. Horisberger.
Tolbutamide-sensitive potassium conductance in the basolateral membrane of A6 cells.
J. Membr. Biol.
134:
181-188,
1993[Medline].
6.
Costantin, J.,
S. Alcalen,
A. De,
S. Otero,
W. P. Dubinsky,
and
S. G. Schultz.
Reconstitution of an inwardly rectifying potassium channel from the basolateral membrane of Necturus enterocytes into planar lipid bilayers.
Proc. Natl. Acad. Sci. USA
86:
5212-5216,
1989[Abstract].
7.
De Weer, P.
Cellular sodium-potassium transport.
In: The Kidney: Physiology and Pathophysiology, edited by D. W. Seldin,
and G. Giebisch. New York: Raven, 1985, p. 31-48.
8.
Dubinsky, W. P.,
O. Mayorga-Wark,
and
S. G. Schultz.
Reconstitution of a KATP channel from basolateral membranes of Necturus enterocytes.
Am. J. Physiol.
269 (Cell Physiol. 38):
C464-C471,
1995
9.
Dubinsky, W. P.,
and
L. B. Monti.
Resolution of apical from basolateral membrane of shark rectal gland.
Am. J. Physiol.
251 (Cell Physiol. 20):
C721-C726,
1986
10.
Garty, H.,
B. Rudy,
and
S. J. Karlish.
A simple and sensitive procedure for measuring isotope fluxes through ion-specific channels in heterogeneous populations of membrane vesicles.
J. Biol. Chem.
258:
13094-13099,
1983
11.
Gullans, S. R.,
and
L. J. Mandel.
Coupling of energy to transport in proximal and distal nephron.
In: The Kidney: Physiology and Pathophysiology (2nd ed.), edited by D. W. Seldin,
and G. Giebisch. New York: Raven, 1992, chapt. 36, p. 1291-1337.
12.
Hardin, C. D.,
L. Raeymaekers,
and
R. J. Paul.
Comparison of endogenous and exogenous sources of ATP in fueling Ca2+ uptake in smooth muscle plasma membrane vesicles.
J. Gen. Physiol.
99:
21-40,
1992[Abstract].
13.
Hurst, A. M.,
J. S. Beck,
R. Laprade,
and
J.-Y. Lapointe.
Na+-pump inhibition downregulates an ATP-sensitive K+ channel in rabbit proximal convoluted tubule.
Am. J. Physiol.
264 (Renal Fluid Electrolyte Physiol. 33):
F760-F764,
1993
14.
Janmey, P. A.
The cytoskeleton and cell signalling: component localization and mechanical coupling.
Physiol. Rev.
78:
763-781,
1998
15.
Kilinc, J. K.,
and
N. Ozer.
Irreversible inactivation of human erythrocyte pyruvate kinase by 2,3-butanedione.
Arch. Biochem. Biophys.
230:
321-326,
1984[Medline].
16.
Läuger, P.
Carrier-mediated ion transport.
Science
178:
24-30,
1972[Medline].
17.
Lederer, W. J.,
E. Niggli,
and
R. W. Hadley.
Sodium-calcium exchange in excitable cells: fuzzy space.
Science
248:
283,
1990[Medline].
18.
Lowry, O. H.,
N. J. Rosebrough,
A. L. Farr,
and
R. J. Randall.
Protein measurement with the Folin phenol reagent.
J. Biol. Chem.
193:
265-275,
1951
19.
Luna, E. J.,
and
A. L. Hitt.
Cytoskeleton-plasma membrane interactions.
Science
258:
955-964,
1992[Medline].
20.
Lynch, R. M.,
and
R. S. Balaban.
Coupling of aerobic glycolysis and Na+-K+-ATPase in renal cell line MDCK.
Am. J. Physiol.
253 (Cell Physiol. 22):
C269-C276,
1987
21.
Mauerer, U. R.,
E. L. Boulpaep,
and
A. S. Segal.
Properties of an inwardly rectifying ATP-sensitive K+ channel on the basolateral membrane of renal proximal tubule.
J. Gen. Physiol.
111:
139-160,
1998
22.
Mauerer, U. L.,
E. L. Bouplaep,
and
A. S. Segal.
Regulation of an inwardly rectifying ATP-sensitive K+ channel on the basolateral membrane of renal proximal tubule.
J. Gen. Physiol.
111:
161-180,
1998
23.
Mercer, R. W.,
and
P. B. Dunham.
Membrane-bound ATP fuels the Na/K pump.
J. Gen. Physiol.
78:
547-568,
1981[Abstract].
24.
Noma, A.
ATP-regulated K channels in cardiac muscle.
Nature
305:
147-148,
1983[Medline].
25.
Parker, J. C.,
and
J. F. Hoffman.
The role of membrane phosphoglycerate kinase in control of glycolytic rate by active cation transport in human red blood cells.
J. Gen. Physiol.
50:
893-916,
1967
26.
Robinson, R. A.,
and
R. H. Stokes.
Electrolyte Solutions (2nd ed.). New York: Academic, 1959.
27.
Schultz, S. G.
Homocellular regulatory mechanisms in sodium-transporting epithelia: avoidance of extinction by "flush-through".
Am. J. Physiol.
241 (Renal Fluid Electrolyte Physiol. 10):
F579-F590,
1981
28.
Schultz, S. G.
Membrane cross-talk in sodium-absorbing epithelial cells.
In: The Kidney: Physiology and Pathophysiology (2nd ed.), edited by D. W. Seldin,
and G. Giebisch. New York: Raven, 1992, p. 287-299.
29.
Semb, S. O.,
and
O. M. Sejersted.
Fuzzy space and control of the Na+,K+-pump rate in heart and skeletal muscle.
Acta Physiol. Scand.
156:
213-225,
1996[Medline].
30.
Sottocasa, G. L.,
B. Kuylenstierna,
L. Ernster,
and
A. Bergstrand.
Separation and some enzymatic properties of the inner and outer membranes of rat liver mitochondria.
Methods Enzymol.
10:
448-463,
1967.
31.
Trafford, A. W.,
M. E. Diaz,
S. C. O'Neill,
and
D. A. Eisner.
Comparison of subsarcolemmal and bulk calcium concentration during spontaneous calcium release in rat ventricular myocytes.
J. Physiol. (Lond.)
488:
577-586,
1995[Abstract].
32.
Tsuchiya, K.,
W. Wang,
G. Giebisch,
and
P. A. Welling.
ATP is a coupling modulator of parallel Na,K-ATPase-K channel activity in the renal proximal tubule.
Proc. Natl. Acad. Sci. USA
89:
6418-6422,
1992[Abstract].
33.
Urbach, V.,
E. Van Kerkhove,
D. Maguire,
and
B. J. Harvey.
Cross-talk between ATP-regulated K+ channels and Na+ transport via cellular metabolism in frog skin principal cells.
J. Physiol. (Lond.)
491:
99-109,
1996[Abstract].
34.
Weiss, J. N.,
and
S. T. Lamb.
Cardiac ATP-sensitive K+ channels.
J. Gen. Physiol.
94:
911-935,
1989[Abstract].