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Departments of 1 Anatomy and Neurobiology and 2 Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont 05405
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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ATP-sensitive K+ (KATP) channels exhibit pharmacological diversity, which is critical for the development of novel therapeutic agents. We have characterized KATP channels in gallbladder smooth muscle to determine how their pharmacological properties compare to KATP channels in other types of smooth muscle. KATP currents were measured in myocytes isolated from gallbladder and mesenteric artery. The potencies of pinacidil, diazoxide, and glibenclamide were similar in gallbladder and vascular smooth muscle, suggesting that the regions of the channel conferring sensitivity to these agents are conserved among smooth muscle types. Activators of protein kinase C (PKC), however, were less effective at inhibiting KATP currents in myocytes from gallbladder than mesenteric artery. The phosphatase inhibitor okadaic acid increased the efficacy of PKC activators and revealed ongoing basal activation of KATP channels by protein kinase A in gallbladder. These results suggest that phosphatases and basal kinase activity play an important role in controlling KATP channel activity.
mesenteric artery; okadaic acid; electrophysiology; adenosine 5'-triphosphate-sensitive potassium channel
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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ATP-SENSITIVE POTASSIUM (KATP) channels
exhibit significant functional and pharmacological diversity, which
reflects, in part, the molecular diversity of the channel structure.
Functional KATP channels are heteromultimers composed of
four pore-forming inwardly rectifying K+ channel (Kir)
subunits of the Kir 6.0 subfamily (Kir 6.1 or 6.2) and
four regulatory sulfonylurea receptor subunits (SUR1, 2A, or 2B) (4). Based on pharmacology, tissue distribution, and expression
of recombinant KATP channels, three broad classes of KATP have been identified: pancreatic 
-cell (Kir 6.2;
SUR1) (7), cardiac-skeletal muscle (Kir 6.2; SUR 2A) (8), and smooth
muscle KATP channels. The molecular composition of smooth
muscle KATP channels is unclear because Kir 6.1, Kir 6.2, SUR 1, and SUR 2B have all been identified in smooth muscle (5, 9, 21).
The functional properties of KATP channels in smooth muscle differ substantially from those in other cell types. Notably, they exhibit a high sensitivity to K+ channel opening drugs such as pinacidil and levcromakalim and exhibit profound modulation by protein kinases (1, 2, 6, 11, 17, 24, 25). Smooth muscle relaxants [e.g., calcitonin gene-related peptide (CGRP) and adenosine], which act through stimulation of protein kinase A (PKA), activate KATP channels in vascular smooth muscle [VSM; mesenteric artery (10, 18), coronary artery (15, 23), cerebral artery (11), and nonvascular smooth muscle (gallbladder)] (24, 25). Smooth muscle constrictors (e.g., neuropeptide Y, angiotensin II, serotonin, acetylcholine, and histamine) that act through stimulation of protein kinase C (PKC) have been shown to inhibit KATP channels in mesenteric and cerebral arteries and esophageal and urinary bladder smooth muscle (1-3, 6, 11, 12). Indeed, PKA and PKC modulation of KATP channels may be a significant mechanism for physiological and pathophysiological regulation of smooth muscle function. Despite the apparent similarity of KATP channel function in various types of smooth muscle, there has been little information in terms of quantitative comparison of KATP channels in this tissue. Uncovering diversity of smooth muscle KATP channel function may point to avenues for the development of smooth muscle type-selective openers of KATP channels that could have significant clinical implications.
We are particularly interested in the regulation of KATP channels in gallbladder smooth muscle (GBSM). Modulation of KATP channels in GBSM could provide a novel means for controlling gallbladder motility, which in turn would affect gallstone formation. KATP channels within GBSM may be an important physiological target of CGRP, which is contained within sensory fibers in the gallbladder wall (13, 14). CGRP induces a membrane potential hyperpolarization and relaxation of intact gallbladder that is blocked by the KATP channel inhibitor glibenclamide (25). CGRP causes gallbladder relaxation through activation of adenylyl cyclase, elevation of cAMP, stimulation of PKA, and activation of KATP channels (24). In contrast to VSM from mesenteric artery (18), the actions of CGRP on gallbladder appear to be limited by high levels of dephosphorylation by a phosphatase, such that KATP currents immediately deactivate upon removal of CGRP (24). Although activators of PKC have been shown to cause pronounced inhibition of KATP channels in smooth muscle from arteries (2, 11), esophagus (6), and urinary bladder (1), their effects on gallbladder are unknown.
The goal of this study was to determine the uniqueness of KATP channels in GBSM, with the ultimate hopes of designing tissue-selective approaches to modulating this channel. The first objective was to provide a pharmacological profile for key K+ channel openers (pinacidil and diazoxide) and glibenclamide on KATP channel currents in isolated myocytes from gallbladder, and the second objective was to determine the effects of activators of PKC on these currents. We found that gallbladder KATP channels resembled those of VSM with regard to their pharmacology. In contrast, however, gallbladder KATP channels were much less sensitive to inhibition by PKC activators than those in VSM and responded differently to phosphatase inhibition.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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GBSM cell isolation. Guinea pigs between 2 and 4 wk old (250-350 g) and of either sex were euthanized with halothane and exsanguinated in a manner approved by the Institutional Animal Care and Use Committee of the University of Vermont. Gallbladders were dissected free from the liver and placed into ice-cold modified Krebs solution (in mM): NaCl 121, KCl 5.9, CaCl2 2.5, MgCl2 1.2, NaHCO3 25, NaH2PO4 1.2, and glucose 8 buffered to pH 7.4 with 95% O2-5% CO2. Gallbladders were transferred to Ca2+-free cell isolation solution containing (in mM): NaCl 55, monosodium glutamate 80, MgCl2 2, KCl 6, glucose 10, and HEPES 10 (adjusted to pH 7.3 with NaOH). Gallbladders were cut open longitudinally and pinned mucosal side up in a Sylgard-coated dish (Dow Corning, Midland, MI). The mucosa was removed with blunted forceps under a dissecting microscope. The remaining tissue was cut into small (1 × 3 mm) strips and placed into cell isolation solution containing: 1 mg/ml BSA, 1 mg/ml papain (23 U/mg; Worthington, Lakewood, NJ), and 1 mg/ml dithioerythritol (Sigma, St. Louis, MO). The mixture was incubated at 37°C for 30-35 min, and the tissue was subsequently transferred to a solution containing 1 mg/ml BSA, 1 mg/ml collagenase (1.01 U/mg; Fluka, Milwaukee, WI), and 100 µM CaCl2 for a further 8-12 min. The tissue was rinsed in cold cell isolation solution and triturated with a glass Pasteur pipette to yield single smooth muscle cells. Cells were stored in glass vials on ice until required and used within 6 h of isolation.
Mesenteric artery smooth muscle cell isolation. Female Sprague-Dawley rats (12-14 wk old) were anesthetized with pentobarbital sodium (25 mg/kg), and the primary branch of the superior mesenteric artery was removed and dissected free from adipose tissue in cell isolation solution. The artery was cut open longitudinally and then enzymatically dissociated in cell isolation solution containing papain (0.5 mg/ml) and dithioerythritol (1 mg/ml) at 37°C for 40 min. The tissue was subsequently transferred to warmed cell isolation solution containing collagenase (0.7 mg/ml; Fluka) and 100 µM CaCl2 for 10 min. The tissue was rinsed and triturated as before to produce isolated mesenteric arterial myocytes. For guinea pig mesenteric myocytes, cells were obtained as above, except arteries were initially incubated in 1 mg/ml papain and 1 mg/ml dithioerythritol at 37°C for 30 min, and then incubated in cell isolation solution containing collagenase (0.5 mg/ml; Sigma blended collagenase type F), 0.5 mg/ml hyaluronidase (Worthington, Lakewood, NJ), and 100 µM CaCl2 for 10 min.
Patch-clamp recordings.
Isolated smooth muscle cells suspended in cell isolation solution were
placed into a recording chamber (1 ml vol) on the stage of an inverted
phase-contrast microscope. Whole cell patch-clamp recordings were
carried out as previously described (24) using an Axopatch 1D amplifier
(Axon Instruments, Foster City, CA). Currents were sampled at 6.6 Hz
with a Digidata A-D board attached to an IBM PC-compatible computer
using Axotape 2 software (Axon Instruments). Electrodes were pulled
from borosilicate glass (Sutter Instruments, Novato, CA), coated with
dental wax, and fire polished to a final resistance of 3-8 M
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Solutions and drugs.
Electrodes were filled with a solution containing (in mM): KCl 102, KOH
38, NaCl 10, MgCl2 1, CaCl2 1, EGTA 10, Na2ATP 0.1, ADP 0.1, Na2GTP 0.2, glucose 10, and HEPES 10 adjusted to pH 7.2 with KOH. Cells were bathed in external
solution containing (in mM): KCl 5, NaCl 135, MgCl2 1, HEPES 10, glucose 10, and CaCl2 0.1 (pH 7.4). When stable,
the bathing solution was exchanged for a solution with the same
composition as above, except that NaCl was substituted for KCl. All
recordings described were performed at 
60 mV in symmetrical 140 mM K+.
-phorbol
12, 13-didecanoate (5PDD), and 1,2-dioctanoyl-sn-glycerol (DOG) were prepared as 1 mM stock solutions in DMSO. Okadaic acid and
adenosine 3',5'-cyclic monophosphothioate
(Rp-cAMPS; Calbiochem, San Diego, CA) were prepared as 100 µM
and 10 mM stock solutions in DMSO and distilled water, respectively.
Unless stated otherwise, all chemicals were purchased from Sigma.
Data analysis. All data are expressed as the mean ± SE of n cells. Glibenclamide-insensitive components of the current were subtracted before analysis with a custom-written analysis program. Glibenclamide-sensitive currents were taken as a measure of KATP currents (24). Concentration-response relationships were fitted with the equation I = Imax/[1 + (K/D)n] where I is current, Imax is maximal current, K is concentration of drug (D) required for half activation, and n is the Hill coefficient. Unpaired Student's t-tests were used to perform statistical analysis, and significance was reported at the 0.05 level.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Pharmacological modulation of KATP currents in GBSM.
Pinacidil is reasonably selective for smooth muscle, as an activator of
KATP channels (19). Diazoxide, in contrast, is equipotent in activating KATP channels in smooth muscle and pancreatic
-cells, but is rather ineffective on KATP channels in
cardiac and skeletal muscle. The effects of these pharmacological
fingerprints are unknown for KATP channels in GBSM. We
therefore tested the effects of pinacidil and diazoxide, as well as the
classic inhibitor, glibenclamide, on KATP currents in GBSM.
60 mV in symmetrical 140 mM K+. Cells
were dialyzed with a pipette solution containing 0.1 mM ATP, 0.2 mM
GTP, and 0.1 mM ADP. Under these conditions, pinacidil activated
KATP currents in gallbladder myocytes in a
concentration-dependent manner between 0.1 and 30 µM (Fig.
1A), with a Hill
coefficient of 1.7 and EC50 of pinacidil at 1.4 µM
(n = 6; Fig. 1B). The KATP channel opener
diazoxide was a less potent activator of KATP channels than
pinacidil (Fig. 2A). The
EC50 concentration for diazoxide calculated from the mean
concentration response data was 97.5 µM, and the Hill coefficient was
1.3 (n = 6 cells; Fig. 2B). Glibenclamide inhibited
KATP currents elicited by 10 µM pinacidil with an
IC50 concentration of 77.6 nM and a Hill coefficient
of 0.94 (n = 6 cells; Fig. 3,
A and B).
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Activators of PKC inhibit KATP currents in smooth muscle
cells from gallbladder and mesenteric artery.
In vascular, urinary bladder, and esophageal smooth muscle, activators
of PKC inhibit pinacidil-induced KATP channel currents (1,
2, 6, 16, 20). The consequence of PKC stimulation on GBSM
KATP channels is not known. The activators of PKC, PMA (100 nM), and the membrane-permeable analog of diacylglycerol, DOG (1 µM),
have been shown to inhibit KATP currents in rabbit mesenteric artery by 86% and 87%, respectively (2). Similarly, 100 nM
PMA inhibited KATP currents in urinary bladder smooth
muscle by 87% (1). Figure 4, B and
C, illustrate inhibition of KATP currents in guinea
pig mesenteric artery myocytes. KATP currents were
inhibited by 22.9 ± 6.4% (n = 6) with 100 nM DOG and 62.7 ± 5.9% (n = 6) with 1 µM DOG, respectively.
KATP currents were also inhibited by 100 nM (36.5 ± 3.1%, n = 5) and 1 µM (84.4 ± 2.9%, n = 6) DOG in rat mesenteric arteries. In contrast, 100 nM DOG had no
significant effect on KATP currents in gallbladder myocytes
(44.9 ± 5.3 pA; control, 45.6 ± 6.3 pA; 100 nM DOG, n = 6).
Increasing the DOG concentration to 1 µM, however, did inhibit gallbladder KATP currents by 34.5 ± 10% (n = 6;
Fig. 4, A and C).
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PDD had no measurable effect
(n = 3) in GBSM, suggesting that the inhibition was mediated
through PKC activation (Fig. 5). These results suggest that
KATP channels in GBSM are less sensitive to modulation by
activators of PKC than those in VSM.
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Actions of phosphatases on KATP currents in GBSM and VSM. Decreased KATP inhibition by PKC activators in GBSM could be due to a disruption in the PKCsignaling pathway as a consequence of differences in KATP channel structure or expression of different PKC isoforms, or, alternatively, could occur if the action of PKC is counteracted by rapid dephosphorylation by phosphatases. Rapid dephosphorylation by phosphatases is supported by the observation that the deactivation of GBSM KATP currents after removal of activators of PKA is rapid (24), compared with VSM (18).
To test the hypothesis that phosphatase activity plays an important role in the regulation of KATP channels, the ability of DOG to inhibit KATP currents in the presence of okadaic acid was examined in gallbladder and mesenteric artery myocytes. DOG-induced inhibition of KATP currents was significantly enhanced in GBSM by okadaic acid, from 3.4 ± 5.8% (n = 5) to 29.9 ± 9.0% (n = 4) with 100 nM DOG, and from 34.5 ± 10% (n = 5) to 65.2 ± 7.4% (n = 6) with 1 µM DOG (Fig. 6, A and C). Similarly, okadaic acid increased inhibition of pinacidil-induced KATP currents by 100 nM DOG in rat mesenteric artery smooth muscle from 36.5 ± 3.1% to 69.4 ± 2% (n = 5), and from 22.9 ± 6.4% (n = 6) to 56.6 ± 15% (n = 3) in guinea pig mesenteric arteries (Fig. 7, A and B). These results suggest that phosphatases play an important role in regulating the activity of KATP channels in smooth muscle.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Pharmacology of GBSM KATP channels. GBSM KATP channels resemble those of VSM with regard to their sensitivity to pinacidil, diazoxide, and glibenclamide. Pinacidil and diazoxide activated KATP currents in gallbladder myocytes with EC50 values of 1 µM and 97 µM, and Hill coefficients of 1.7 and 1.3, respectively. These values are similar to those reported in rabbit mesenteric artery smooth muscle cells where pinacidil activated KATP currents with an EC50 of 1 µM and a Hill coefficient of 1.5 (19), and rat colonic smooth muscle where pinacidil activated KATP currents with an EC50 of 1.3 µM (17). Diazoxide has been shown to open KATP channels in rabbit mesenteric artery smooth muscle with an EC50 of 37 µM and a Hill coefficient of 1.0 (19) and in myocytes isolated from rat colon with an EC50 of 34.2 µM (17). In this study, glibenclamide inhibited gallbladder KATP currents with an IC50 of 77.6 nM and a Hill coefficient of 0.9, which is also comparable to the IC50 of 100 nM and the Hill coefficient of 0.8 reported for glibenclamide in VSM (19). The K+ channel openers pinacidil and diazoxide, and glibenclamide, are thought to bind to the SUR subunit of the KATP channel to modulate channel activity. This is supported by observations showing that recombinant KATP channels expressing different SUR subunits differ with regard to their sensitivity to pinacidil, diazoxide, and glibenclamide (7, 9). Mutations that disrupt the integrity of two nucleotide binding folds (NBF1 and NBF2) of the SUR subunit abolish sensitivity of recombinant KATP channels to K+ channel-opening drugs (21). Kir 6.2 channels without SUR do not exhibit sensitivity to K+ channel-opening drugs (22), consistent with SUR being the target of these drugs. We have demonstrated here that KATP channels in GBSM have similar sensitivities to pinacidil, diazoxide, and glibenclamide as those in VSM and colon, suggesting that SUR is likely to be conserved among smooth muscle types. The molecular identity of SUR in smooth muscle, however, is unclear, because mRNA for both SUR1 and SUR 2B are found in VSM (3). In terms of their sensitivity to K+ channel openers and to glibenclamide, however, smooth muscle KATP channels resemble recombinant Kir 6.2/SUR 2B channels (9).
Inhibition of smooth muscle KATP channels by PKC: role of phosphatases. KATP channels in VSM are regulated by PKA and PKC. Vasoconstrictors such as histamine, serotonin, angiotensin II, acetylcholine, and neuropeptide Y that stimulate PKC cause a reduction in KATP channel activity (2, 11, 12), whereas vasodilators that stimulate PKA, such as CGRP and adenosine, activate KATP channels (10, 15, 18). Nitrovasodilators that activate PKG such as nitric oxide and sodium nitroprusside have not been demonstrated to activate KATP currents in VSM (18, 23). In non-VSM of the urinary bladder and esophagus, KATP channels are inhibited by activators of PKC (1, 6). The effects of PKC activators on KATP channels in GBSM were previously not known.
We have demonstrated here that GBSM KATP channels are less sensitive to inhibition by PKC activators than those in either guinea pig or rat mesenteric artery, suggesting there may be differences in KATP channel modulation in GBSM and VSM. The phosphatase inhibitor, okadaic acid, increased the effectiveness of PKC activators to inhibit KATP currents in GBSM and VSM, suggesting that phosphatases play an important role in regulating the activity of KATP channels. However, even in the presence of okadaic acid, PKC activators were more effective at inhibiting KATP channels in myocytes from mesenteric arteries than from gallbladder. This observation suggests that other factors in addition to phosphatases are responsible for the apparent difference in PKC activator efficacy. Phosphatase inhibition activated a glibenclamide-sensitive current in GBSM that was blocked by the PKA inhibitor Rp-cAMPs (Fig. 6, A and D). In contrast, phosphatase inhibition by okadaic acid did not increase KATP currents in myocytes from mesenteric arteries, but, in fact, slightly decreased the KATP current (Fig. 7A). One explanation of these results is that PKA activation of KATP currents is ongoing in GBSM, but not in VSM, and phosphatase inhibition enhances this activation by decreasing dephosphorylation of the PKA site. Our results suggest that, under physiological conditions, KATP channel activity is dependent on a balance between phosphorylation by PKA and PKC, and dephosphorylation of their respective phosphorylation sites by phosphatases. It is unknown what sites on KATP channels or other unknown regulatory proteins are phosphorylated by PKA and PKC to cause physiological effects. There are several putative PKC phosphorylation sites on both SUR and Kir. Interestingly, there are three putative PKC phosphorylation sites at the COOH-terminal region of Kir 6.1 that are absent in Kir 6.2, making the Kir subunit a possible phosphorylation target of PKC, and may explain why there are tissue-specific differences in regulation of KATP channels by PKC activators. Similarly, there are four putative PKA phosphorylation sites on the KATP channel, two on SUR, and two on Kir. In conclusion, we have demonstrated that gallbladder KATP channels have a similar pharmacological profile as VSM KATP channels with respect to their sensitivity to pinacidil, diazoxide, and glibenclamide. Furthermore, our results support a key role of phosphatases in the regulation of KATP channel activity in GBSM and VSM.| |
ACKNOWLEDGEMENTS |
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We thank Gerald Herrera and George Wellman for critical appraisal of the manuscript.
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FOOTNOTES |
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This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-26995, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-45410, and National Heart, Lung, and Blood Institute Grant HL-44455.
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.
Address for reprint requests and other correspondence: G. M. Mawe, Dept. of Anatomy and Neurobiology, College of Medicine, Univ. of Vermont, Burlington, VT 05405 (E-mail: gmawe{at}zoo.uvm.edu).
Received 2 August 1999; accepted in final form 22 December 1999.
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REFERENCES |
|---|
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Bonev, AD,
and
Nelson MT.
Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary bladder smooth muscle.
Am J Physiol Cell Physiol
265:
C1723-C1728,
1993
2.
Bonev, AD,
and
Nelson MT.
Vasoconstrictors inhibit ATP-sensitive K+ channels in arterial smooth muscle through protein kinase C.
J Gen Physiol
108:
315-323,
1996
3.
Bradley, KK,
Eckman DM,
Nelson MT,
and
Horrowitz B.
Molecular forms of K-ATP in vascular smooth muscle cells (Abstract).
Biophys J
76:
78,
1999.
4.
Clement, JP,
Kunjilwar K,
Gonzalez G,
Schwanstecher M,
Panten U,
Aguilar-Bryan L,
and
Bryan J.
Association and stoichiometry of K(ATP) channel subunits.
Neuron
18:
827-838,
1997[Web of Science][Medline].
5.
Gopalakrishnan, M,
Whiteaker KL,
Molinari EJ,
Davis-Taber R,
Scott VE,
Shieh CC,
Buckner SA,
Milicic I,
Cain JC,
Postl S,
Sullivan JP,
and
Brioni JD.
Characterization of the ATP-sensitive potassium channels (KATP) expressed in guinea pig bladder smooth muscle cells.
J Pharmacol Exp Ther
289:
551-558,
1999
6.
Hatakeyama, N,
Wang Q,
Goyal RK,
and
Akbarali HI.
Muscarinic suppression of ATP-sensitive K+ channel in rabbit esophageal smooth muscle.
Am J Physiol Cell Physiol
268:
C877-C885,
1995
7.
Inagaki, N,
Gonoi T,
Clement JP,
Namba N,
Inazawa J,
Gonzalez G,
Aguilar-Bryan L,
Seino S,
and
Bryan J.
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
Science
270:
1166-1170,
1995
8.
Inagaki, N,
Gonoi T,
Clement JP,
Wang CZ,
Aguilar-Bryan L,
Bryan J,
and
Seino S.
A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
Neuron
16:
1011-1017,
1996[Web of Science][Medline].
9.
Isomoto, S,
Kondo C,
Yamada M,
Matsumoto S,
Higashiguchi O,
Horio Y,
Matsuzawa Y,
and
Kurachi Y.
A novel sulfonylurea receptor forms with BIR (Kir6.2), a smooth muscle type ATP-sensitive K+ channel.
J Biol Chem
271:
24321-24324,
1996
10.
Kleppisch, T,
and
Nelson MT.
Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase.
Proc Natl Acad Sci USA
92:
12441-12445,
1995
11.
Kleppisch, T,
and
Nelson MT.
ATP-sensitive K+ currents in cerebral arterial smooth muscle: pharmacological and hormonal modulation.
Am J Physiol Heart Circ Physiol
269:
H1634-H1640,
1995
12.
Kubo, M,
Quayle JM,
and
Standen NB.
Angiotensin II inhibition of ATP-sensitive K+ currents in rat arterial smooth muscle cells through protein kinase C.
J Physiol (Lond)
503:
489-496,
1997
13.
Maggi, CA,
Santicioli P,
Renzi D,
Patacchini R,
Surrenti C,
and
Meli A.
Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin.
Gastroenterology
96:
1093-1101,
1989[Web of Science][Medline].
14.
Mawe, GM,
and
Gershon MD.
Structure, afferent innervation, and transmitter content of ganglia of the guinea pig gallbladder: relationship to the enteric nervous system.
J Comp Neurol
283:
374-390,
1989[Web of Science][Medline].
15.
Miyoshi, H,
and
Nakaya Y.
Calcitonin gene-related peptide activates the K+ channels of vascular smooth muscle cells via adenylate cyclase.
Basic Res Cardiol
90:
332-336,
1995[Web of Science][Medline].
16.
Nelson, MT,
and
Quayle JM.
Physiological roles and properties of potassium channels in arterial smooth muscle.
Am J Physiol Cell Physiol
268:
C799-C822,
1995
17.
Pluja, L,
Yokoshiki H,
and
Sperelakis N.
Evidence for presence of ATP-sensitive K+ channels in rat colonic smooth muscle cells.
Can J Physiol Pharmacol
76:
1166-1170,
1998[Web of Science][Medline].
18.
Quayle, JM,
Bonev AD,
Brayden JE,
and
Nelson MT.
Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A.
J Physiol (Lond)
475:
9-13,
1994
19.
Quayle, JM,
Bonev AD,
Brayden JE,
and
Nelson MT.
Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery.
Am J Physiol Cell Physiol
269:
C1112-C1118,
1995
20.
Quayle, JM,
Nelson MT,
and
Standen NB.
ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.
Physiol Rev
77:
1165-1232,
1997
21.
Schwanstecher, M,
Sieverding C,
Dorschner H,
Gross I,
Aguilar-Bryan L,
Schwanstecher C,
and
Bryan J.
Potassium channel openers require ATP to bind to and act through sulfonylurea receptors.
EMBO J
17:
5529-5535,
1998[Web of Science][Medline].
22.
Tucker, SJ,
Gribble FM,
Zhao C,
Trapp S,
and
Ashcroft FM.
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
Nature
387:
179-183,
1997[Medline].
23.
Wellman, GC,
Quayle JM,
and
Standen NB.
ATP-sensitive K+ channel activation by calcitonin gene-related peptide and protein kinase A in pig coronary arterial smooth muscle.
J Physiol (Lond)
507:
117-129,
1998
24.
Zhang, L,
Bonev AD,
Mawe GM,
and
Nelson MT.
Protein kinase A mediates activation of ATP-sensitive K+ currents by CGRP in gallbladder smooth muscle.
Am J Physiol Gastrointest Liver Physiol
267:
G494-G499,
1994
25.
Zhang, L,
Bonev AD,
Nelson MT,
and
Mawe GM.
Activation of ATP-sensitive potassium currents in guinea-pig gallbladder smooth muscle by the neuropeptide CGRP.
J Physiol (Lond)
478:
483-491,
1994
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 J. Y. Jun, I. D. Kong, S. D. Koh, X. Y. Wang, B. A. Perrino, S. M. Ward, and K. M. Sanders Regulation of ATP-sensitive K+ channels by protein kinase C in murine colonic myocytes Am J Physiol Cell Physiol, September 1, 2001; 281(3): C857 - C864. [Abstract] [Full Text] [PDF]
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J. M. Hemming, F. A. Guarraci, T. A. Firth, L. J. Jennings, M. T. Nelson, and G. M. Mawe Actions of histamine on muscle and ganglia of the guinea pig gallbladder Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G622 - G630. [Abstract] [Full Text] [PDF]
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M. J. Pozo, G. J. Perez, M. T. Nelson, and G. M. Mawe Ca2+ sparks and BK currents in gallbladder myocytes: role in CCK-induced response Am J Physiol Gastrointest Liver Physiol, January 1, 2002; 282(1): G165 - G174. [Abstract] [Full Text] [PDF]
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