Angiotensin II stimulates basolateral K channels in rat
cortical collecting ducts
Yuan
Wei and
Wenhui
Wang
Department of Pharmacology, New York Medical College, Valhalla, New
York 10595
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ABSTRACT |
We used the patch-clamp technique
to study the effects of angiotensin II (ANG II) on basolateral K
channels in cortical collecting ducts (CCDs). Application of ANG II
(100 pM-100 nM) increased the activity of basolateral 18-pS K
channels. This effect of ANG II was completely abolished by losartan,
which is an antagonist of type 1 angiotensin (AT1)
receptors. In contrast, inhibition of type 2 angiotensin
(AT2) receptors did not block the stimulatory effect of ANG
II. Also, application of ANG II significantly increased intracellular
Ca2+ concentrations, which were measured with fura 2 dye.
To explore the role of Ca2+-dependent pathways in the
regulation of basolateral K channels, the effects of ANG II on channel
activity were examined in the presence of arachidonyltrifluoromethyl
ketone to inhibit phospholipase A2 (PLA2),
GF-109203X [a protein kinase C (PKC) inhibitor], and NG-nitro-L-arginine methyl ester
(L-NAME) to inhibit nitric oxide synthase. Inhibition of
either PLA2 or PKC did not block the effect of ANG II on
basolateral K-channel activity. However, the stimulatory effect of ANG
II was absent in the CCDs treated with L-NAME. Moreover, addition of the membrane-permeant 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) not only increased channel activity but
also abolished the stimulatory effect of ANG II on channel activity. We
conclude that ANG II increases basolateral K-channel activity via the
stimulation of AT1 receptors, and the stimulatory effect of
ANG II is mediated by a nitric oxide-dependent cGMP pathway.
guanosine 3',5'-cyclic monophosphate; nitric oxide; angiotensin
type 1 receptor; potassium secretion
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INTRODUCTION |
BASOLATERAL K CHANNELS
PLAY an important role in generating cell-membrane potential in
the cortical collecting ducts (CCDs; Refs. 7,
33). Because Na reabsorption and K secretion in the CCDs
are electrogenic processes (24, 30), a change in the
cell-membrane potential is expected to have effects on Na reabsorption
and K secretion (17, 25, 26, 29). Moreover, basolateral K
channels can serve as potential routes for K to enter the cell when the
cell-membrane potential exceeds the K equilibrium potential
(28). There are at least three types of K channels, which
are measured here according to inside-out and cell-attached patches,
respectively: small conductance, 18 and 27 pS; intermediate
conductance, 28 and 67 pS; and large conductance, 85 and 148 pS.
Although the regulatory mechanisms of these types of K channels are
different, all three are activated by guanosine 3',5'-cyclic
monophosphate (cGMP)-dependent protein kinase (10, 18,
32).
The production of cGMP can be stimulated by nitric oxide (NO), which is
a potent activator of soluble quanylate cyclase (GC; Ref.
14). We previously demonstrated that NO links
apical Na transport to basolateral K-channel activity: an increase in
apical Na entry leads to augmentation of the intracellular
Ca2+ concentration [Ca2+]i, which
in turn stimulates the activity of Ca2+-dependent NO
synthase (NOS). As a consequence, NO increases cGMP generation, which
further activates basolateral K channels (20). This
suggests that the Ca2+-NO-cGMP pathway plays an important
role in the regulation of basolateral K-channel activity. However, it
is not clear which hormone regulates basolateral K channels via a
cGMP-dependent pathway. Because the stimulation of type 1 angiotensin
(AT1) receptors has been shown to increase
[Ca2+]i in renal tubules (4) and
AT1 receptors are also present in CCDs (9), it
is possible that angiotensin (ANG) II may have an effect on basolateral
K channels via Ca2+-NO-cGMP pathways. Therefore, in the
present study, we explored the role of ANG II in the regulation of
basolateral K channels.
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METHODS |
Preparation of CCDs.
Male pathogen-free Sprague-Dawley rats (age 5-6 wk) were used in
the experiments. The rats were purchased from Taconic Farms (Germantown, NY) and were fed a normal rat chow. We also used rats that
were fed a high-K diet (10%, wt/wt) in some experiments. Because the
responses of basolateral K channels to ANG II were the same for rats on
normal rat chow, data were pooled. The body weight of the rats used for
the experiments was 100-120 g. Rats were killed by cervical
dislocation, and the kidneys were removed immediately. Several thin
(<1 mm) slices of kidney were cut and placed in ice-cold Ringer
solution until dissection. The dissection was carried out at room
temperature, and two watchmakers' forceps were used to isolate the
single CCD. To immobilize the tubules, they were placed on a 5 × 5-mm cover-glass that was coated with D-polylysin (Becton
Dickinson, Bedford, MA) and were then transferred to a 1-ml chamber
that was mounted on an inverted Nikon microscope. The CCDs were
superfused with HEPES-buffered NaCl-Ringer solution, and the
temperature of the chamber was maintained at 37°C by circulation of
warm water around the chamber. We followed previously described methods
to prepare the basolateral membrane for patch-clamp experiments. Briefly, after the CCD was split open, the intercalated cell was removed to gain access to the lateral membrane principal cell. In addition, we also patched the CCD that was treated with 1% collagenase. Because the effects of ANG II on the basolateral K
channels from the collagenase-treated and untreated CCDs were identical, we pooled the data.
Patch-clamp technique.
Single-channel current was recorded by an Axon 200A patch-clamp
amplifier and was low-pass filtered at 1 kHz through an eight-pole Bessel filter (model 902LPF; Frequency Devices, Haverhill, MA). The
data were digitized by an Axon interface (Digidata 1200) and stored in
an IBM-compatible Pentium II computer. We used pClamp software system
6.04 (Axon Instruments, Burlingame, CA) to generate an all-point
histogram, which was then fitted to calculate the channel activity.
Channel activity was defined as NPo, a product of channel number (N) and open probability
(Po) that was calculated from data samples of
60-s duration in the steady state as
where ti is the fractional open time
spent at each of the observed current levels. No efforts were made to
determine whether an increase in channel activity results from a change
in N or Po.
Measurement of
[Ca2+]i.
[Ca2+]i was measured with fura
2-acetoxymethyl ester (Molecular Probes, Eugene, OR). Fluorescence was
imaged digitally with an intensified video-imaging system that included
a SIT 68 camera, controller, and HR 1000 video monitor. The exiting and
emitted light passed through a ×40 fluorite objective (numerical
aperture, 1.30; Nikon, Melville, NY). We followed methods published
previously (20) to measure and calculate the
[Ca2+]i.
Experimental solution and statistics.
The pipette solution contained (in mM) 140 KCl, 1.8 MgCl2,
and 10 HEPES (pH 7.4). The bath solution was composed of (in mM) 140 NaCl, 5 KCl, 1.8 CaCl2, 1.8 MgCl2, 5 glucose,
and 10 HEPES (pH 7.4). Herbimycin A, GF-10239X, and
arachidonyltrifluoromethyl ketone (AACOCF3) were purchased
from Biomol (Plymouth Meeting, PA) and were dissolved in DMSO solution.
The final concentration of DMSO was <0.1% and had no effect on
channel activity. Ionomycin, ANG II, 8-bromo-cGMP, losartan, PD-123319,
and NG-nitro-L-arginine methyl ester
(L-NAME) were purchased from Sigma Chemical (St. Louis,
MO). Data are shown as means ± SE, and paired Student's
t-test was used to determine the significance between the
two groups. Statistical significance was taken as P < 0.05.
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RESULTS |
In our previous study, we patched the lateral membranes of
principal cells using an approach that removed the intercalated cell
next to the principal cell (35) and identified a 27-pS K
channel in cell-attached patches in the CCD. When the bath and pipette
solutions were switched to a symmetrical 140-mM KCl solution, the
channel conductance in inside-out patches was 18 pS. This 18-pS K
channel can be found in 35% of patches in the CCDs obtained from rats
that were fed normal rat chow and 52% from rats on a high-K diet.
Because the Po was 0.5-0.8, it was assumed
that the 18-pS K channel is one of the major K channels that
contributes to basolateral K conductance in CCDs. This conclusion is
also supported by experiments performed on collagenase-treated CCDs. We
observed the 18-pS K channels in 11 of 31 cell-attached patches. Moreover, the Po was 0.4-0.7 and was not
significantly different from that observed for channels from
collagenase-untreated CCDs. Also, it has been found that the
response of the 18-pS K channel to ANG II in both tubule preparations
was the same. Therefore, we pooled the data obtained from both
collagenase-treated and untreated CCDs.
Several investigations have demonstrated that ANG II receptors are
expressed in CCDs (4, 9); however, it has not been explored whether ANG II is involved in the regulation of the transport function in CCDs. Therefore, we examined the effect of ANG II on the
activity of basolateral 18-pS K channels. Figure
1A is a representative
recording that shows the effect of 100 nM ANG II on the basolateral K
channel from a cell-attached patch. It is apparent that ANG II
significantly increased NPo from 0.76 ± 0.2 under control conditions to 1.74 ± 0.25 (n = 7). Figure 1B is a dose-response curve of the ANG II effect,
which demonstrates that ANG II stimulates the 18-pS K channel at a
concentration of 100 pM and that the stimulatory effect of ANG II
reaches its plateau at 100 nM. To determine which type of ANG II
receptor was responsible for mediating the effect of ANG II on the
basolateral K channels, we examined the effects of 100 nM ANG II on
basolateral 18-pS K channels in the presence of losartan, an antagonist
of AT1 receptors (1 µM) and PD-123319 (1 µM), a
selective antagonist of AT2 receptors. Addition of either
losartan or PD-123319 had no significant effect on channel activity
(Fig. 2). However, inhibition of
AT2 receptors did not abolish the stimulatory effect of ANG II on basolateral K channels. Figure 3 is
a representative recording that shows the effect of ANG II on 18-pS K
channels in the presence of an AT2-receptor inhibitor.
Clearly, PD-123319 did not block the effect of ANG II on channel
activity, because addition of ANG II increased
NPo from 0.75 ± 0.2 to 1.75 ± 0.22 (n = 9). In contrast, inhibition of AT1
receptors completely abolished the effect of ANG II on 18-pS K channels
(see Fig. 2), because application of 100 nM ANG II failed to increase
channel activity (control, 0.70 ± 0.2; ANG II, 0.8 ± 0.2;
n = 5). This suggests that the effects of ANG II on
channel activity are mediated by stimulation of AT1
receptors.

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Fig. 1.
A: effect of angiotensin II (ANG II) on
basolateral K-channel activity in a cell-attached patch. Time course of
the experiment is shown (top); two parts of the trace
indicated by numbers are expanded (middle and
bottom) to illustrate the fast resolution. Time when 100 nM
ANG II was added to the bath is indicated (arrow). Pipette holding
potential was 30 mV (hyperpolarization of cell membrane potential by
30 mV), and the channel closed level is indicated (C). B:
dose-response curve of effect of ANG II on basolateral K-channel
activity. Experimental number for each group was 5-10. Data were
normalized using the equation [NPo
(experimental)/NPo (control)], where
N is channel number and Po is open
probability. *Data are significantly different from the control value
(without ANG II). AII, angiotensin II.
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Fig. 2.
Effects of 100 nM ANG II on basolateral 18-pS K channels
in the presence of PD-123319 [an inhibitor of type 2 angiotensin
(AT2) receptors] and losartan [an inhibitor of type 1 angiotensin (AT1) receptors], respectively. *Result is
significantly different from the control value.
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Fig. 3.
Effects of 100 nM ANG II on basolateral K channels in a
cell-attached patch in the presence of PD-123319. Time course of the
experiment is shown (top); two parts of the trace are
expanded (middle and bottom) to demonstrate the
fast time resolution. Channel closed level is indicated (C); the
pipette holding potential was 30 mV.
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This notion is also supported by experiments in which the effect of ANG
II on [Ca2+]i was determined with fura 2 dye
(Fig. 4A). Figure
4B summarizes results from four measurements (4 tubules
obtained from 3 rats) showing that addition of ANG II transiently
increased the [Ca2+]i from the control value
of 75 ± 8 to 126 ± 15 nM. Therefore, it is possible
that the effect of ANG II was mediated by an increase in the
[Ca2+]i. From our previous studies, we
identified three possible Ca2+-dependent signal
transduction pathways: PKC, phospholipase A2 (PLA2), and neuronal (n)NOS. All three pathways have been
demonstrated to regulate either the apical or basolateral K-channel
activity in CCDs (33). First, we investigated the
possibility that Ca2+-dependent PKC may mediate the effect
of ANG II, because PKC has been shown to mediate the stimulatory effect
of ANG II on bicarbonate transport in the proximal tubule
(16) and increase basolateral 18-pS K-channel activity in
CCDs (19). Figure 5
summarizes results from five experiments in which the effect of ANG II
on 18-pS K-channel activity was examined in the presence of the PKC
inhibitor GF-109203X (5 µM). We confirmed the previous findings that
inhibition of PKC slightly decreased the basal level of channel
activity (19). However, inhibition of PKC did not block
the stimulatory effect of ANG II on basolateral K-channel activity, and
NPo increased from 0.70 ± 0.15 to
1.60 ± 0.25. We next tested the effect of ANG II on channel
activity in the presence of a PLA2 inhibitor. As shown in
Fig. 5, inhibition of PLA2 with AACOCF3 (5 µM) had no significant effect on channel activity. Furthermore, ANG
II could still increase channel activity from 0.93 ± 0.18 to
1.66 ± 0.23 in the presence of AACOCF3. The notion
that the effect of ANG II on basolateral 18-pS K channels was not
mediated by a PLA2-dependent pathway is also indicated by
experiments in which addition of 10 µM arachidonic acid did not
increase the channel activity (data not shown).

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Fig. 4.
A: this original trace shows the effect of 100 nM ANG II on intracellular Ca2+ concentration
([Ca2+]i) in the cortical collecting ducts
(CCDs). B: data obtained from 4 tubules are summarized to
show the effect of ANG II.
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Fig. 5.
Effect of 100 nM ANG II on basolateral 18-pS K channels
in the presence of GF-109203X (a PKC inhibitor) and
arachidonyltrifluoromethyl ketone [AACOCF3, a
phospholipase A2 (PLA2) inhibitor]. *Result
was significantly different from the control value.
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After determining that the effect of ANG II was not mediated by PKC- or
PLA2-dependent pathways, we examined the effect of ANG II
on channel activity in the presence of L-NAME. Because inhibition of NOS significantly decreased channel activity, we selected
patches in which a high channel activity was observed to examine the
effects of ANG II. Figure 6 is a
representative recording that demonstrates the effect of ANG II (100 nM) on channel activity in the presence of 0.2 mM L-NAME.
Addition of L-NAME decreased channel activity, and
NPo decreased from 1.3 ± 0.15 to 0.70 ± 0.1 (n = 5). Moreover, inhibition of NOS abolished
the effect of ANG II on channel activity, and ANG II did not increase NPo (control, 0.7 ± 0.1; ANG II, 0.80 ± 0.1). We have previously shown that the stimulatory effect of NO was
mediated by the cGMP-dependent pathway (18). To determine
whether the effect of ANG II on 18-pS K channels resulted from an
increase in cGMP formation, we examined the effect of ANG II on channel
activity after the CCDs were challenged by 8-bromo-cGMP. Addition of
200 µM 8-bromo-cGMP stimulated channel activity and increased
NPo from 0.6 ± 0.1 to 1.65 ± 0.2 (Fig. 7). Moreover, the effects of ANG II
were absent in the presence of cGMP. Figure
8 is a representative recording that
demonstrates the effect of 100 nM ANG II on 18-pS K channels in the
presence of 0.2 mM 8-bromo-cGMP. Before addition of ANG II,
NPo was 1.42 ± 0.2 (n = 6). Addition of 100 nM ANG II did not increase
NPo (1.45 ± 0.2). Thus the effect of cGMP
and ANG II was not additive, which suggests that the stimulatory effect
of ANG II is the result of an increase in cGMP formation in the CCDs.

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Fig. 6.
Effect of 100 nM ANG II on basolateral K-channel activity
in the presence of 0.2 mM
NG-nitro-L-arginine methyl ester
(L-NAME). Time course of the experiments is shown
(top); three parts of the data indicated by numbers are
expanded (middle and bottom) to show fast time
resolution. Pipette holding potential was 30 mV; channel closed line
is indicated (C).
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Fig. 7.
A channel recording that demonstrates the effect of 200 µM 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) on
basolateral K-channel activity in a cell-attached patch. Time course of
the experiment is shown (top); two numbered areas of the
data are expanded (middle and bottom) to
demonstrate channel activity at a fast resolution. Holding potential
was 30 mV; channel closed level is indicated (C).
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Fig. 8.
A channel recording that shows the effect of 100 nM ANG
II on basolateral K-channel activity in the presence of 200 µM
8-bromo-cGMP. Experiment was performed in a cell-attached patch with
holding potential of 30 mV. Time course of the experiment is shown
(top); two parts of the data indicated by numbers are
expanded (middle and bottom) to demonstrate the
fast resolution.
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DISCUSSION |
The main findings of the present study are that the stimulation of
AT1 receptors increases the activity of basolateral 18-pS K
channels and that the stimulatory effect of ANG II is mediated by a
cGMP-dependent pathway. A large body of evidence indicates that ANG II
plays an important role in the regulation of Na reabsorption in renal
tubules (6, 8, 15, 27). ANG II stimulates bicarbonate reabsorption in the proximal tubule via a PKC-dependent pathway (16). In the thick ascending limb, ANG II inhibits the
apical 70-pS K channel by increasing 20-hydroxytetraenoic acid release (21) and decreasing bicarbonate reabsorption by cytochrome
P-450 metabolites of arachidonic acid
(8).
The effects of ANG II on epithelial membrane transport are mediated by
the interaction of two types of ANG II receptors: AT1 and
AT2. It is well documented that both AT1 and
AT2 receptors are expressed in the kidney (4, 9,
36). However, AT1 receptors are most likely to be
responsible for the effects of ANG II on renal tubule transport
(2). The highest expression level of AT1
receptors was identified in the proximal tubules, and the next-highest
level of AT1 receptors was found in the thick ascending limb (4). A large body of evidence has strongly indicated
that AT1 receptors are also present in the cortical and
outer medullary collecting duct (4, 9). Also, using RT-PCR
technique, the presence of AT2-receptor mRNA has been found
in the collecting ducts (36). Therefore, it is
conceivable that ANG II plays an important role in regulation of the
transport function in collecting ducts. This speculation has been
confirmed by our present study: ANG II activates the basolateral 18-pS
K channels. Although the effect of ANG II on basolateral K channels
other than the 18-pS channel has not yet been investigated, it is
possible that ANG II may also stimulate the intermediate- and
large-conductance K channels in the basolateral membrane of CCDs,
because all three types of basolateral K channels are activated by cGMP
(10, 32). Therefore, it is expected that stimulation of
AT1 receptors would increase basolateral K conductance.
Basolateral K channels serve several cell functions in CCDs. First, the
channels are responsible for generating cell-membrane potentials
(7, 33). As both K secretion and Na reabsorption in CCDs
are electrogenic processes, an alteration in cell-membrane potential is
expected to have an effect on Na absorption. Indeed, it has been
demonstrated that inhibition of the basolateral K conductance reduces
Na transport in CCDs (29). Second, K channels play a role
in basolateral K recycling. Stimulation of Na-K-ATPase has been shown
to increase basolateral K conductance in renal tubules including
proximal tubules and CCDs (3, 11, 23). The coupling
between Na-K-ATPase activity and basolateral K conductance is important
for maintenance of a constant intracellular K concentration during
stimulation of Na-K-ATPase activity by a variety of factors. Third,
basolateral K channels can provide an alternative route for K to enter
the cells across the basolateral membrane when the cell-membrane
potential exceeds the K equilibrium potential (28).
Relevant to the third role of K channels in CCDs is the observation
that K enters the cell across the basolateral membrane via a
Na-K-ATPase-independent pathway, presumably via basolateral K channels,
when the aldosterone level is high (28).
The effects of ANG II on basolateral K channels are mediated by
AT1 receptors, because losartan, a specific
AT1-receptor antagonist, abolished the stimulatory effect
of ANG II on basolateral K channels. Moreover, we have demonstrated
that application of ANG II increases the
[Ca2+]i in CCDs. The effect of ANG II on the
[Ca2+]i is generally believed to be mediated
by AT1 receptors (2). Therefore, it is
conceivable that a Ca2+-dependent signal transduction
pathway is responsible for the effects of ANG II. The ANG II-induced
increase in [Ca2+]i is only a modest 50 nM in
the present experiment. However, it is possible that the increase in
[Ca2+]i is compartmentalized and is higher in
the close proximity of the basolateral K channels than the amount
indicated by the mean increase in [Ca2+]i.
Moreover, it is also possible that NOS is colocalized with basolateral
K channels. Accordingly, stimulation of ANG II receptors could produce
an elevated NO concentration for activation of the basolateral K
channels. It has been reported that nNOS and the N-methyl-D-aspartate receptors are physically
linked by the PSD95-Dlg-zona occludens domain (1, 5).
Furthermore, it is likely that a 50-nM increase in
[Ca2+]i is sufficient to stimulate the 18-pS
K channel. We have previously demonstrated that a 50-nM increase in
[Ca2+]i significantly stimulates the
basolateral 18-pS K channel in CCDs (20). It has been
demonstrated that the activity of nNOS is very sensitive to changes in
[Ca2+]i in the range of 100-200 nM and
that a 100-nM increase in Ca2+ concentration stimulates NO
production and GC activation by tenfold (12).
Therefore, it is possible that a slight increase in
[Ca2+]i could be sufficient to activate
basolateral K channels. There are at least three
Ca2+-dependent signal transduction pathways in CCDs:
PLA2, PKC, and NOS (34). The observations that
neither inhibition of PLA2 nor blocking of PKC had an
influence on the effects of ANG II excludes the possibility that these
pathways mediate the effects of ANG II on basolateral K channels.
Two lines of evidence suggest that the effects of ANG II on basolateral
K channels were mediated by a Ca2+-dependent NO pathway:
1) addition of ANG II elevated the
[Ca2+]i, and 2) inhibition of NOS
abolished the stimulatory effect of ANG II on K channels. Figure
9 is a model of a principal cell in the
CCD that illustrates a possible mechanism by which ANG II could
increase the basolateral K-channel activity. The stimulation of
AT1 receptors increases [Ca2+]i,
which in turn activates Ca2+-dependent nNOS and,
accordingly, increases NO production. This leads to activation of
soluble GC, increased cGMP generation, and augmentation of
basolateral K-channel activity. This hypothesis is supported by our
previous observation that nNOS was specifically expressed in principal
cells of CCDs (34). Moreover, it has been demonstrated
that soluble GC is present in CCDs (22). The notion that
cGMP mediates the effects of ANG II on basolateral K channels is also
supported by the finding that ANG II did not increase channel activity
in the presence of the membrane-permeant 8-bromo-cGMP. The effect of
cGMP is most likely mediated by cGMP-dependent protein kinase G (PKG),
because PKG has been demonstrated to activate 18-pS K channels
(32). This speculation is also consistent with the finding
that although the ANG II-induced increase in
[Ca2+]i was transient, the stimulatory effect
of ANG II on basolateral 18-pS K channels was stable during our
experimental period (10-15 min). It is possible that when K
channels are activated by PKG, the channel activity can be maintained
as active for a certain amount of time even if
[Ca2+]i returns to the control value from its
peak value. A similar finding that NO-cGMP signaling mediates the
effect of ANG II on Na-K-ATPase in the proximal tubule has been
reported (37).

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Fig. 9.
A model of a CCD principal cell that illustrates the
mechanism by which ANG II stimulates the activity of basolateral 18-pS
K channels. nNOS, neuronal nitric oxide synthase; PKG, protein kinase
G.
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AT1 receptors have been shown to be expressed in both the
apical and basolateral membranes (9). Because our
experiments were carried out in split-open tubules, it is not clear
whether the effect of ANG II on basolateral K channels was the result of stimulation of the basolateral and apical AT1 receptors.
However, it is possible that the effects of ANG II were the result of
stimulation of basolateral AT1 receptors. The effects of
ANG II on basolateral K channels in the regulation of Na reabsorption
and K secretion have not been explored. However, it is possible that
the stimulatory effect of ANG II on basolateral K channels could
potentially increase Na reabsorption in CCDs, because hyperpolarization
increases the electrochemical gradient for luminal Na entering the cell
across the apical membrane. This hypothesis has been supported by a
microperfusion study (31) in which application of ANG II
stimulated the amiloride-sensitive Na transport in the late distal
tubule, which includes the initial CCDs. In addition to stimulation of
basolateral K channels, cGMP inhibits the 28-pS Na channel in the inner
medullary collecting duct (IMCD; Ref. 13). Therefore, it
is likely that the effect of cGMP on Na transport depends on the
nephron segment: cGMP may indirectly stimulate Na absorption by
increasing the driving force for Na in the CCDs and inhibit Na
absorption by blocking the 28-pS Na channels in the IMCD.
We conclude that ANG II stimulates basolateral 18-pS K channels by
activation of AT1 receptors and that the stimulatory effect of ANG II on channel activity is mediated by a cGMP-dependent pathway.
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ACKNOWLEDGEMENTS |
This work was supported by National Institutes of Health Grant
DK-47402.
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FOOTNOTES |
Address for reprint requests and other correspondence: W. H. Wang, Dept. of Pharmacology, New York Medical College, Valhalla, NY
10595 (E-mail: wenhui_wang{at}nymc.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.
August 13, 2002;10.1152/ajprenal.00211.2002
Received 5 June 2002; accepted in final form 31 July 2002.
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