1.Expression of ATP-sensitive potassium channel and sulfonylurea receptor in neonate and adult rat tissues.
So Yeong LEE ; Hang LEE ; Mun Han LEE ; Pan Dong RYU
The Korean Journal of Physiology and Pharmacology 2001;5(5):433-441
The ATP-sensitive potassium (KATP) channel is a member of inward rectifier potassium channel (Kir) that is inhibited by intracellular ATP and functions in close relation to sulfonylurea receptors (SUR). Although the molecular mechanism and physiological function of KATP channels are well understood, the expression pattern during development or treatment with the channel modulators such as glybenclamide is little known. In this work, we determined mRNA levels of a KATP channel (Kir6.2) and a sulfonylurea receptor (SUR2) in rat tissues by RNase protection assay. Levels of Kir6.2 and SUR2 mRNA in the rat brain and skeletal muscle were higher in adult (90-120 days) than in neonate (2-8 days), whereas those in the heart were not much different between neonate (2-8 days) and adult (90-120 days). In addition, none of KATP channel modulators (opener, pinacidil and nicorandil; blocker, glybenclamide) affected the Kir6.2 mRNA levels in the heart, brain and skeletal muscle. The results indicate that the expression of Kir and SUR genes can vary age-dependently, but the expression of Kir is not dependent on the long-term treatment of channel modulators. The effect of the channel modulators on mRNA level of SUR is remained to be studied further.
Adenosine Triphosphate
;
Adult*
;
Animals
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Brain
;
Glyburide
;
Heart
;
Humans
;
Infant, Newborn*
;
KATP Channels
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Muscle, Skeletal
;
Nicorandil
;
Pinacidil
;
Potassium Channels*
;
Potassium Channels, Inwardly Rectifying
;
Potassium*
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Rats*
;
Ribonucleases
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RNA, Messenger
;
Sulfonylurea Receptors
2.Cause of Intracellular ATP dependency on Zn2++ Blockade of KATP Channels in Pancreatic Beta Cells.
Korean Journal of Aerospace and Environmental Medicine 1999;9(1):77-82
In order to clarify the cause of intracellular ATP dependency on Zn2+ blockade of KATP channels in pancreatic beta cells, we investigated the KATP channel activity during external Zn2+ application using voltage clamp technique. Cultured beta cells were used for patch-clamp experiment. When 3 mM glucose was applied in bath, KATP channel activity was increased transiently by externally applied Zn2+ in the cell-attached mode and was recoverable. The KATP channel activity was, however, consistently increased by Zn2+ application during the 0 mM glucose in bath. Inside-out mode, internally applied Zn2+ elicited no response on the KATP channels. Another divalent cation, Mn2+, didn't have any effect on the KATP channels. Therefore, This effect, so-called external glucose-dependency on Zn2+ blockade of the KATP channels, might be due to intracellular Zn2+ metabolism which induces ATP consumption. This appears to be a mechanism that the Zn2+ blockade of the KATP channels in the pancreatic beta cells depends on the intracellular ATP concentration.
Adenosine Triphosphate*
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Baths
;
Glucose
;
Insulin-Secreting Cells*
;
KATP Channels*
;
Metabolism
3.Neonatal Diabetes Caused by Activating Mutations in the Sulphonylurea Receptor.
Diabetes & Metabolism Journal 2013;37(3):157-164
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic beta-cells play a crucial role in insulin secretion and glucose homeostasis. These channels are composed of two subunits: a pore-forming subunit (Kir6.2) and a regulatory subunit (sulphonylurea receptor-1). Recent studies identified large number of gain of function mutations in the regulatory subunit of the channel which cause neonatal diabetes. Majority of mutations cause neonatal diabetes alone, however some lead to a severe form of neonatal diabetes with associated neurological complications. This review focuses on the functional effects of these mutations as well as the implications for treatment.
Adenosine Triphosphate
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Glucose
;
Homeostasis
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Insulin
;
KATP Channels
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Polyphosphates
;
Potassium
5.Involvement of ATP-sensitive potassium channels in proliferation and differentiation of rat preadipocytes.
Yao-Hui WANG ; Hai-Yan ZHENG ; Na-Lin QIN ; Shang-Bin YU ; Sheng-Yuan LIU
Acta Physiologica Sinica 2007;59(1):8-12
This paper was aimed to investigate the effects of ATP-sensitive potassium channels on the proliferation and differentiation of rat preadipocytes. We examined the expression of sulphonylurea receptor 2 (SUR2) mRNA in preadipocytes and adipocytes obtained by inducing for 5 d and the effects of the inhibitor (glibenclamide) and opener (diazoxide) of ATP-sensitive potassium channels on the expression of SUR2 mRNA in preadipocytes by real-time PCR. Preadipocyte proliferation and cell cycle were measured by MTT spectrophotometry and flow cytometer. The content of intracellular lipid was measured by oil red O staining, cell diameter was determined by Image-Pro Plus 5.0 software and the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA was estimated by RT-PCR. SUR2 mRNA was expressed in both preadipocytes and adipocytes obtained by inducing for 5 d, and the expression in adipocytes was obviously higher than that in preadipocytes. Glibenclamide inhibited the expression of SUR2 mRNA in preadipocyte, promoted preadipocyte proliferation in a dose-dependent manner, increased the cell percentages in G(2)/M + S phase, increased lipid content, augmented adipocyte diameter, and promoted the expression of PPAR-gamma mRNA. But the actions of diazoxide were contrary to those of glibenclamide. These results suggest that ATP-sensitive potassium channels regulate the proliferation and differentiation of preadipocytes, and PPAR-gamma is probably involved in the effect of ATP-sensitive potassium channels.
ATP-Binding Cassette Transporters
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genetics
;
metabolism
;
Adipocytes
;
cytology
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Animals
;
Cell Differentiation
;
physiology
;
Cell Proliferation
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Cells, Cultured
;
KATP Channels
;
physiology
;
Male
;
Obesity
;
pathology
;
PPAR gamma
;
metabolism
;
Potassium Channels, Inwardly Rectifying
;
genetics
;
metabolism
;
RNA, Messenger
;
genetics
;
metabolism
;
Rats
;
Rats, Sprague-Dawley
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Receptors, Drug
;
genetics
;
metabolism
;
Sulfonylurea Receptors
6.K(ATP) channel action in vascular tone regulation: from genetics to diseases.
Wei-Wei SHI ; Yang YANG ; Yun SHI ; Chun JIANG
Acta Physiologica Sinica 2012;64(1):1-13
ATP-sensitive potassium (K(ATP)) channels are widely distributed in vasculatures, and play an important role in the vascular tone regulation. The K(ATP) channels consist of 4 pore-forming inward rectifier K(+) channel (Kir) subunits and 4 regulatory sulfonylurea receptors (SUR). The major vascular isoform of K(ATP) channels is composed of Kir6.1/SUR2B, although low levels of other subunits are also present in vascular beds. The observation from transgenic mice and humans carrying Kir6.1/SUR2B channel mutations strongly supports that normal activity of the Kir6.1/SUR2B channel is critical for cardiovascular function. The Kir6.1/SUR2B channel is regulated by intracellular ATP and ADP. The channel is a common target of several vasodilators and vasoconstrictors. Endogenous vasopressors such as arginine vasopressin and α-adrenoceptor agonists stimulate protein kinase C (PKC) and inhibit the K(ATP) channels, while vasodilators such as β-adrenoceptor agonists and vasoactive intestinal polypeptide increase K(ATP) channel activity by activating the adenylate cyclase-cAMP-protein kinase A (PKA) pathway. PKC phosphorylates a cluster of 4 serine residues at C-terminus of Kir6.1, whereas PKA acts on Ser1387 in the nucleotide binding domain 2 of SUR2B. The Kir6.1/SUR2B channel is also inhibited by oxidants including reactive oxygen species allowing vascular regulation in oxidative stress. The molecular basis underlying such a channel inhibition is likely to be mediated by S-glutathionylation at a few cysteine residues, especially Cys176, in Kir6.1. Furthermore, the channel activity is augmented in endotoxemia or septic shock, as a result of the upregulation of Kir6.1/SUR2B expression. Activation of the nuclear factor-κB dependent transcriptional mechanism contributes to the Kir6.1/SUR2B channel upregulation by lipopolysaccharides and perhaps other toll-like receptor ligands as well. In this review, we summarize the vascular K(ATP) channel regulation under physiological and pathophysiological conditions, and discuss the importance of K(ATP) channel as a potentially useful target in the treatment and prevention of cardiovascular diseases.
ATP-Binding Cassette Transporters
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genetics
;
physiology
;
Animals
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Endotoxemia
;
metabolism
;
physiopathology
;
Humans
;
KATP Channels
;
genetics
;
physiology
;
Mice
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Mice, Transgenic
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Muscle, Smooth, Vascular
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metabolism
;
physiology
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Potassium Channels, Inwardly Rectifying
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genetics
;
physiology
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Receptors, Drug
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genetics
;
physiology
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Shock, Septic
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metabolism
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physiopathology
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Sulfonylurea Receptors
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Vasoconstriction
;
physiology
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Vasodilation
;
physiology
;
Vasomotor System
;
physiology
7.Differential Changes of ATP-sensitive Potassium Channel Current after Hypoxia-reperfusion Treatment in Mouse Neuroblastoma 2a (N2a) Cell.
The Korean Journal of Physiology and Pharmacology 2002;6(4):183-186
Ischemic damage is one of the most serious problems. The openers of KATP channel have been suggested to have an effect to limit the ischemic damage. However, it is not yet clear how KATP channels of a cell correspond to hypoxic damage. To address the question, N2a cells were exposed to two different hypoxic conditions as follows: 6 hours hypoxia followed by 3 hours reperfusion and 12 hours hypoxia followed by 3 hours reperfusion. As the results, 6 hours hypoxic treatment increased glibenclamide-sensitive basal KATP current activity (approximately 6.5-fold at 0 mV test potential) when compared with nomoxic condition. In contrast, 12 hours hypoxic treatment induced a relatively smaller change in the KATP current density (2.5-fold at 0 mV test potential). Additionally, in experiments where KATP channels were opened using diazoxide, the hypoxia for 6 hours significantly increased the current density in comparison to control condition (p < 0.001). Interestingly, the augmentation in the KATP current density reduced after exposure to the 12 hours hypoxic condition (p < 0.001). Taken together, these results suggest that KATP channels appear to be recruited more in cells exposed to the 6 hours hypoxic condition and they may play a protective role against hypoxia-reperfusion damage within the time range.
Animals
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Anoxia
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Diazoxide
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Glyburide
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KATP Channels
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Mice*
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Neuroblastoma*
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Potassium Channels*
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Potassium*
;
Reperfusion
8.Expression of KATP in pulmonary artery smooth muscle cells under hypoxia-hypercapnia condition and the relationship with p38 MAPK pathway.
Ying-Chun MA ; ; Lin-Jing HUANG ; Meng-Xiao ZHENG ; Yuan-Yuan WANG ; Lei YING ; Wan-Tie WANG
Acta Physiologica Sinica 2014;66(3):283-288
The aim of the present study is to investigate the expressions of ATP-sensitive K(+) channels (KATP) in pulmonary artery smooth muscle cells (PASMCs) and the relationship with p38 MAPK signal pathway in rats. Male SD rat PASMCs were cultured in vitro, and a model of hypoxia and hypercapnia was reconstructed. PASMCs were divided to normal (N), hypoxia-hypercapnia (H), hypoxia-hypercapnia+DMSO incubation (HD), hypoxia-hypercapnia+SB203580 (inhibitor of p38 MAPK pathway) incubation (HS) and hypoxia-hypercapnia+Anisomycin (agonist of p38 MAPK pathway) incubation (HA) groups. Western blot was used to detect the protein expression of SUR2B and Kir6.1; semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of SUR2B and Kir6.1. The results demonstrated that: (1) Compared with N, H, HD and HS groups, the expressions of Kir6.1 mRNA and protein in PASMCs of HA group were decreased significantly (P < 0.01), but there were no differences among N, H, HD and HS groups (P > 0.05); (2) Compared with N group, the expressions of SUR2B mRNA and protein in H, HD, HS and HA groups were increased significantly (P < 0.05), but there were no differences among H, HD, HS and HA groups (P > 0.05). The results imply that: (1) Hypoxia-hypercapnia, SB203580 didn't change the expressions of Kir6.1 mRNA and protein in PASMCs, but Anisomycin decreased the expressions of Kir6.1 mRNA and protein, so Kir6.1 may be regulated by the other subfamily of MAPK pathway; (2) Hypoxia-hypercapnia raised SUR2B mRNA and protein expressions in PASMCs, but SB203580 and Anisomycin did not affect the changes, so the increasing of SUR2B mRNA and protein induced by hypoxia-hypercapnia may be not depend on p38 MAPK pathway.
Animals
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Anisomycin
;
pharmacology
;
Cell Hypoxia
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Cells, Cultured
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Hypercapnia
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Imidazoles
;
pharmacology
;
KATP Channels
;
metabolism
;
MAP Kinase Signaling System
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Male
;
Myocytes, Smooth Muscle
;
metabolism
;
Pulmonary Artery
;
cytology
;
Pyridines
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Sulfonylurea Receptors
;
metabolism
;
p38 Mitogen-Activated Protein Kinases
;
antagonists & inhibitors
9.Effect of Cisapride on ATP-sensitive K Channel of Ventricular Cell.
Sung Gi MOON ; Byeong Hyun IN ; Won Ho KIM ; Jae Ki KO
Korean Circulation Journal 1998;28(1):76-81
BACKGROUND: It has been generally accepted that Cisapride (Prepulsid?or propulsid?), a widely used gastrointestinal prokinetic agent, is associated with Torsades de Points, a life-threatening arrhythmia. Recently, cisapride-induced APD (action potential duration)-prolongation was inhibited by glibenclamide, a KATP channel blocker. But the direct effect of cisapride on K(ATP) channels has not been studied until now. Therefore, we investigated cisapride's effects on KATP channels of isolated rat ventricular myocytes. METHODS: After the isolation of rat ventricular myocytes, we analysed the single channel current with patch pipettes. The method of analysis was the student t-test. RESULTS: 1) Cisapride (10(-6) M- 10(-4) M) inhibited KATP channel opening without changing channel conductance Ki was about 20micronM, and Hill coefficient was 0.75. 2) Cisapride inhibited pinacidil-induced KATP channel opening in the cell attached mode. CONCLUSIONS: These results suggest that cisapride-induced APD prolongation and arrythmic effects may be partly related to KATP channel inhibition.
Animals
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Arrhythmias, Cardiac
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Cisapride*
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Glyburide
;
Humans
;
KATP Channels
;
Muscle Cells
;
Rats
10.ATP-sensitive potassium channels: novel potential roles in Parkinson's disease.
Jie ZENG ; Gang WANG ; Sheng-Di CHEN
Neuroscience Bulletin 2007;23(6):370-376
The ATP-sensitive potassium (K(ATP)) channels which extensively distribute in diverse tissues (e.g. vascular smooth muscle, cardiac cells, and pancreas) are well-established for characteristics like vasodilatation, myocardial protection against ischemia, and insulin secretion. The aim of this review is to get insight into the novel roles of K(ATP) channels in Parkinson's disease (PD), with consideration of the specificities K(ATP) channels in the central nervous system (CNS), such as the control of neuronal excitability, action potential, mitochondrial function and neurotransmitter release.
Humans
;
KATP Channels
;
drug effects
;
physiology
;
Mitochondria
;
metabolism
;
Parkinson Disease
;
metabolism
;
therapy