Putative subunits of the rat mesangial KATP: a type 2B sulfonylurea receptor and an inwardly rectifying K+ channel.

  title={Putative subunits of the rat mesangial KATP: a type 2B sulfonylurea receptor and an inwardly rectifying K+ channel.},
  author={Balazs Szamosfalvi and Pedro Cort{\'e}s and Rebecca S Alviani and Kenichi Asano and Bruce L. Riser and Gary Zasuwa and Jerry Yee},
  journal={Kidney international},
  volume={61 5},
BACKGROUND Sulfonylurea agents exert their physiological effects in many cell types via binding to specific sulfonylurea receptors (SUR). SUR couple to inwardly-rectifying K+ channel (Kir6.x) to form tetradimeric ATP-sensitive K+ channels (KATP). The SUR subunits confer ATP-sensitivity on KATP and also provide the binding sites for sulfonylureas and other pharmacological agents. Our previous work demonstrated that the exposure of mesangial cells (MC) to sulfonylureas generated profound effects… 

Localization of the sulphonylurea receptor subunits, SUR2A and SUR2B, in rat renal tubular epithelium.

The regulatory subunits of the K(ATP) channel in the rat kidney are SUR2A and SUR2B; they also are candidate regulatory sub units for the mitochondrial K(atp) channel.

Rat mesangial α-endosulfine

Mesangial cell expression of ENSA, the gene encoding α-endosulfine, and its regulation by glucose are investigated to find potential roles as a regulator of metabolism and contractility via mesangial cells K ATP.

Different Localization of ATP Sensitive K+ Channel Subunits in Rat Testis

Different localizations of the KatP channel subunits in the cell membrane and membranous organelles of spermatogenic cells and Sertoli cells indicated the complex and multiple functions of KATP channels in rat testis.

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

  • Ming ZhouHui-Jing He H. Abe
  • Biology, Medicine
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • 2007
SUR2A and SUR2B are not only the regulatory subunits of sarcolemmal KATP channels but may also function as regulatory sub units in mitochondrial KatP channels and play important roles in cardioprotection.

Effects of sulfonylureas, alpha-endosulfine counterparts, on glomerulosclerosis in type 1 and type 2 models of diabetes.

Long-term treatment with sulfonylureas completely prevents glomerular injury in insulin-deficient diabetes in rats, but this protective effect is not demonstrable in an insulin-resistant model of the disease.

α-Endosulfine in Diabetic Nephropathy

Significant SULF-induced metabolic effects in cultured rat mesangial cells (MCs), including alterations in mesangia matrix metabolism and MC contractility, independent of their effect on the ambient level of glycemia are documented.

Glibenclamide prevents increased extracellular matrix formation induced by high glucose concentration in mesangial cells.

Chronic Glib treatment at low concentrations markedly diminishes the high glucose-induced enhanced accumulation of extracellular matrix components by suppression of steady-state PAI-1 transcriptional activity.

Immunohistochemical, pharmacovigilance, and omics analyses reveal the involvement of ATP-sensitive K+ channel subunits in cancers: role in drug–disease interactions

Immunohistochemistry/omics/pharmacovigilance data reveal the role of the Kir6.1/2-Sur2A/B subunits as a drug target in breast/renal cancers and in C.S. Cantu’ syndrome, and elevated expression of the Sur2A subunit was found in proliferating cells in two animal models of cancer.

Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells

Low dosage/concentration Glib prevents HG-induced collagen accumulation in MC by enhancing collagen catabolism in a cAMP-PKA-mediated PAI-1 inhibition.

Effects of long-term elevated glucose on collagen formation by mesangial cells.

The studies suggest that prolonged exposure to HG results in PKC-delta-driven collagen accumulation by MCs mediated by PAI-1 but independent of TGF-beta.

ATP-Sensitive K+ channel modulator binding to sulfonylurea receptors SUR2A and SUR2B: opposite effects of MgADP.

The data suggest that SUR2A and 2B represent the opener receptors of cardiac and vascular smooth muscle KATP channels, respectively, and show that MgADP is an important modulator of opener binding to SUR.

C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K+ Channels

It is suggested that the C-terminal segment of SUR2A possesses an inhibitory effect on NBD2-mediated ADP-induced channel activation, which underlies the differential effects of ADP and diazoxide on KATP channels containing different SURs.

A Novel Sulfonylurea Receptor Forms with BIR (Kir6.2) a Smooth Muscle Type ATP-sensitive K+ Channel*

The reverse transcription-polymerase chain reaction analysis showed that mRNA of this clone was ubiquitously expressed in diverse tissues, including brain, heart, liver, urinary bladder, and skeletal muscle, suggesting that this novel isoform of sulfonylurea receptor is a subunit reconstituting the smooth muscle KATP channel.

Stoichiometry of sulfonylurea-induced ATP-sensitive potassium channel closure.

It is concluded that occupation of one of the four SUR sites per channel complex is sufficient to induce KATP channel closure and that the C terminus of SURs does not affect sulfonylurea affinity and sensitivity.

Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea‐sensitive but ATP‐insensitive K+ channel.

The K+ channel composed of the sulphonylurea receptor 2B and an inwardly rectifying K+Channel subunit Kir6.1 is not a classical ATP‐sensitive K+channel but closely resembles the nucleotide diphosphate‐dependent K+ channels in vascular smooth muscle cells.

SUR2 subtype (A and B)‐dependent differential activation of the cloned ATP‐sensitive K+ channels by pinacidil and nicorandil

It is strongly suggested that this short part of SUR2A and SUR2B may play a critical role in the action of nicorandil on the vascular type classical KATP channel.

Coexpression with the inward rectifier K(+) channel Kir6.1 increases the affinity of the vascular sulfonylurea receptor SUR2B for glibenclamide.

The data show that SUR2B, previously considered to be a low-affinity SUR, has a rather high affinity for GBC, and the recombinant channel exhibits the same GBC affinity as the opener-sensitive K(+) channel in vascular tissue, which suggests that occupation of all four GBC sites per channel is required for channel closure.

Toward understanding the assembly and structure of KATP channels.

The cloning and reconstitution of the subunits of these channels demonstrate they are heteromultimers of inwardly rectifying potassium channel subunits (KIR6.x) and sulfonylurea receptors (SUR), members of the ATP-binding cassette (ABC) superfamily.

Different Binding Properties and Affinities for ATP and ADP among Sulfonylurea Receptor Subtypes, SUR1, SUR2A, and SUR2B*

The results suggest that their different properties may explain, in part, the differential regulation of KATP channel subtypes, and the C-terminal 42 amino acids affect the physiological roles of SUR2A and SUR2B by changing the nucleotide-binding properties of their NBFs.