Localization of Sulfonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Heart

Zhou, Ming; He, Huijing; Suzuki, Ryoji; Liu, Ke-Xiang; Tanaka, Osamu; Sekiguchi, Masaki; Kawahara, Katsumasa; Abe, Hiroshi

doi:10.1369/jhc.6a7104.2007

Cited by 33 publications

(33 citation statements)

References 37 publications

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“…As the combination of channel and regulatory molecules of K ATP channels, several examples have been reported as follows: Kir6.2 with SUR1 in pancreatic β cells (Inagaki et al 1995a), Kir6.2 with SUR2A in cardiac muscle (Inagaki et al 1996), or Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B in cardiac muscles (Lacza et al 2003;Seino and Miki 2004;Zhou et al 2007a), and Kir6.1 with SUR2B in the smooth muscle of blood vessels (Yamada et al 1997;Seino and Miki 2003). RT-PCR analysis showed SUR2B mRNA to be ubiquitously expressed in diverse tissues, including the kidney , and also to be localized in rat vascular smooth muscle (Wang et al 2003) and rat mesangial cells (Szamosfalvi et al 2002).…”

Section: Discussionmentioning

confidence: 99%

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Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Zhou

Tanaka

et al. 2008

Tohoku J. Exp. Med.

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ATP-sensitive K + (K ATP ) channels in the kidney are considered to play roles in regulating membrane potential according to changes in the intracellular ATP concentration. They are composed of two types of subunits; the pore subunits (Kir6.1, Kir6.2), which are members of the inwardly rectifying K + channel family, and the regulatory subunits, the sulphonylurea receptors, which belong to the ATP-binding cassette (ABC) superfamily. The sulphonylurea receptors (SURs) are receptors of sulphonylureas widely used for the treatment of type 2 diabetes mellitus. The SURs are divided into two isoforms, SUR1 and SUR2, the latter was further divided into SUR2A and SUR2B. In the present study, we have investigated the mRNA expression by RT-PCR assay, and protein expression profi les by immunoblotting, immunohistochemistry, and immunoelectron microscopy with anti SUR2A and anti SUR2B antibodies. RT-PCR detected the presence of mRNA transcripts of the SUR2A and SUR2B, while SUR1 mRNA was barely detected. In immunoblotting, SUR2A protein was detected distinctly in the microsomal fraction, weakly in the mitochondrial fraction and at negligible level in the cell membrane fraction. In contrast, the SUR2B protein was detected intensely in the microsomal fraction, with a low level in the mitochondrial fraction and scarcely in the cell membrane fraction. In immunohistochemistry SUR2A and SUR2B proteins were widely distributed in renal tubular epithelial cells, glomerular mesangial cells, and the endothelium and the smooth muscle of blood vessels. In immunoelectron microscopy, the immunoreactivity was localized in the endoplasmic reticulum and mitochondria throughout the epithelial cells for SUR2A, and dominantly in the apical cytoplasm of the cells for SUR2B. In conclusion, the regulatory subunits of the K ATP channel in the rat kidney are SUR2A and SUR2B; they also are candidate regulatory subunits for the mitochondrial K ATP channel.ATP-sensitive K + channel; sulphonylurea receptor; immunohistochemistry; immunoelectron microscopy; kidney.Tohoku

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Section: Discussionmentioning

confidence: 99%

“…The antisera were purifi ed by immunoaffi nity column chromatography for SUR2A and protein-A chromatography column for SUR2B before immunoblotting and immunohistochemical assay. The specifi cities of these antisera were confi rmed (Zhou et al 2007a).…”

Section: Anti-sur2 Antiseramentioning

confidence: 90%

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Zhou

Tanaka

et al. 2008

Tohoku J. Exp. Med.

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“…1) SUs may have direct effects on sulfonylurea 2A (SUR2A) and sulfonylurea 2B (SUR2B) receptors expressed in cardiomyocytes and heart smooth muscle cells, which might have negative effects. 2) Treatment with SUs is associated with hypoglycemia, which is proarrhytmogenic and may increase CV events (22,23).…”

Section: Clinical Effectsmentioning

confidence: 99%

“…Furthermore, patients who experience hypoglycemia often fear a tight glycemic control of the disease which may have implications for quality of life and the treatment to target. Moreover, hypoglycemia is associated with increased risk for CV diseases because it is proarrhytmogenic (22), which might explain increased mortality during intense glucose control with compounds associated with high risk of hypoglycemia (23).…”

Section: Limitationsmentioning

confidence: 99%

Are Sulfonylureas Less Desirable Than DPP-4 Inhibitors as Add-on to Metformin in the Treatment of Type 2 Diabetes?

Åhrén

2011

Curr Diab Rep

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Sulfonylureas (SUs) are commonly used as add-on to metformin in treatment of type 2 diabetes in patients who are insufficiently controlled by metformin alone. They have good efficacy and have shown to prevent microvascular complications. However, treatment with SUs is also associated with a high frequency of hypoglycemia, increased body weight, and a high risk of secondary failure. During recent years, dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as alternatives to SUs. They show similar efficacy as SUs but with lower risk of hypoglycemia, and reduction or no change in body weight, and if confirmed in humans, they may preserve islet function and thereby minimizing the risk for secondary failure. Their limitation at present is the lack of longterm (>5 years) experience on durability and safety. Overall, therefore, the conclusion emerges that SUs are less desirable than DPP-4 inhibitors in management of hyperglycemia in type 2 diabetes.3

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“…19 Another layer of complexity regarding the role of K ATP in IPC has been added by the recent finding that SUR2A is expressed not only in the sarcolemma but also the mitochondria of cardiomyocytes. 127 It remains to be seen whether functional SUR-containing K ATP channels will be found in the mitochondria and, if so, what role they play in IPC or general cardiac cellular physiology.…”

Section: K Atp Channels and Cardioprotectionmentioning

confidence: 99%

The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the K _ATP Channel

Burke

Mutharasan

Ardehali

2008

Circulation Research

109

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Abstract-ATP-binding cassette (ABC) proteins are highly conserved and widely expressed throughout nature and found in all organisms, both prokaryotic and eukaryotic. They mediate myriad critical cellular processes, from nutrient import to toxin efflux using the energy derived from ATP hydrolysis. Most ABC proteins mediate transport of substances across lipid membranes. However, there are atypical ABC proteins that mediate other processes. These include, but are not limited to, DNA repair (bacterial MutS), ion transport (cystic fibrosis transmembrane receptor), and mRNA trafficking (yeast Elf1p). The sulfonylurea receptor (SUR) is another atypical ABC protein that regulates activity of the potassium ATP channel (K ATP ). K ATP is widely expressed in nearly all tissues of higher organisms and couples cellular energy status to membrane potential. K ATP is particularly important in the regulation of insulin secretion from pancreatic ␤-cells and in regulating action potential duration in muscle cells. SUR is indispensable for normal channel function, and mutations in genes encoding SURs increase the susceptibility to diabetes, myocardial infarction, and heart failure. Here, we review the structure and function of ABC proteins and discuss SUR, its regulation of the K ATP channel, and its role in cardiovascular disease. (Circ Res. 2008;102:164-176.)

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Localization of Sulfonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Heart

Cited by 33 publications

References 37 publications

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Are Sulfonylureas Less Desirable Than DPP-4 Inhibitors as Add-on to Metformin in the Treatment of Type 2 Diabetes?

The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the K _ATP Channel

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Localization of Sulfonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Heart

Cited by 33 publications

References 37 publications

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Are Sulfonylureas Less Desirable Than DPP-4 Inhibitors as Add-on to Metformin in the Treatment of Type 2 Diabetes?

The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the K ATP Channel

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The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the K _ATP Channel