scholarly journals Sulfonylureas Correct Trafficking Defects of ATP-sensitive Potassium Channels Caused by Mutations in the Sulfonylurea Receptor

2004 ◽  
Vol 279 (12) ◽  
pp. 11096-11105 ◽  
Author(s):  
Feifei Yan ◽  
Chia-Wei Lin ◽  
Elizabeth Weisiger ◽  
Etienne A. Cartier ◽  
Grit Taschenberger ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Sulfonylurea Receptor ◽  
Trafficking Defects

scholarly journals Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations

2016 ◽  
Vol 291 (42) ◽  
pp. 21971-21983 ◽  
Author(s):  
Gregory M. Martin ◽  
Emily A. Rex ◽  
Prasanna Devaraneni ◽  
Jerod S. Denton ◽  
Kara E. Boodhansingh ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Sulfonylurea Receptor ◽  
Sulfonylurea Receptor 1 ◽  
Pharmacological Correction ◽  
Trafficking Defects

ATP-sensitive and inwardly rectifying potassium channels in smooth muscle

1997 ◽  
Vol 77 (4) ◽  
pp. 1165-1232 ◽  
Author(s):  
J. M. Quayle ◽  
M. T. Nelson ◽  
N. B. Standen
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Potassium Channels ◽  
Membrane Conductance ◽  
Katp Channels ◽  
Muscle Membrane ◽  
Sulfonylurea Receptor ◽  
Kir Channels ◽  
Inwardly Rectifying

The properties and roles of ATP-sensitive (KATP) and inwardly rectifying (KIR) potassium channels are reviewed. Potassium channels regulate the membrane potential of smooth muscle, which controls calcium entry through voltage-dependent calcium channels, and thereby contractility through changes in intracellular calcium. The KATP channel is likely to be composed of members of the inward rectifier channel gene family (Kir6) and sulfonylurea receptor proteins. The KIR channels do not appear to be as widely distributed as KATP channels in smooth muscle and may provide a mechanism by which changes in extracellular K+ can alter smooth muscle membrane potential, and thereby arterial diameter. The KATP channels contribute to the resting membrane conductance of some types of smooth muscle and can open under situations of metabolic compromise. The KATP channels are targets of a wide variety of vasodilators and constrictors, which act, respectively, through adenosine 3',5'-cyclic monophosphate/protein kinase A and protein kinase C. The KATP channels are also activated by a number of synthetic vasodilators (e.g., diazoxide and pinacidil) and are inhibited by the oral hypoglycemic sulfonylurea drugs (e.g., glibenclamide). Together, KATP and KIR channels are important regulators of smooth muscle function and represent important therapeutic targets.

scholarly journals Carbamazepine as a Novel Small Molecule Corrector of Trafficking-impaired ATP-sensitive Potassium Channels Identified in Congenital Hyperinsulinism

2013 ◽  
Vol 288 (29) ◽  
pp. 20942-20954 ◽  
Author(s):  
Pei-Chun Chen ◽  
Erik M. Olson ◽  
Qing Zhou ◽  
Yelena Kryukova ◽  
Heidi M. Sampson ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Misfolding ◽  
Secretory Pathway ◽  
Transmembrane Domain ◽  
Congenital Hyperinsulinism ◽  
Sulfonylurea Receptor ◽  
Channel Activity ◽  
Channel Trafficking ◽  
Channel Function ◽  
Trafficking Defects

ATP-sensitive potassium (KATP) channels consisting of sulfonylurea receptor 1 (SUR1) and the potassium channel Kir6.2 play a key role in insulin secretion by coupling metabolic signals to β-cell membrane potential. Mutations in SUR1 and Kir6.2 that impair channel trafficking to the cell surface lead to loss of channel function and congenital hyperinsulinism. We report that carbamazepine, an anticonvulsant, corrects the trafficking defects of mutant KATP channels previously identified in congenital hyperinsulinism. Strikingly, of the 19 SUR1 mutations examined, only those located in the first transmembrane domain of SUR1 responded to the drug. We show that unlike that reported for several other protein misfolding diseases, carbamazepine did not correct KATP channel trafficking defects by activating autophagy; rather, it directly improved the biogenesis efficiency of mutant channels along the secretory pathway. In addition to its effect on channel trafficking, carbamazepine also inhibited KATP channel activity. Upon subsequent removal of carbamazepine, however, the function of rescued channels was recovered. Importantly, combination of the KATP channel opener diazoxide and carbamazepine led to enhanced mutant channel function without carbamazepine washout. The corrector effect of carbamazepine on mutant KATP channels was also demonstrated in rat and human β-cells with an accompanying increase in channel activity. Our findings identify carbamazepine as a novel small molecule corrector that may be used to restore KATP channel expression and function in a subset of congenital hyperinsulinism patients.

scholarly journals Neonatal Diabetes Caused by Mutations in Sulfonylurea Receptor 1: Interplay between Expression and Mg-Nucleotide Gating Defects of ATP-Sensitive Potassium Channels

2010 ◽  
Vol 31 (5) ◽  
pp. 779-779
Author(s):  
Qing Zhou ◽  
Intza Garin ◽  
Luis Castaño ◽  
Jesús Argente ◽  
Ma. Teresa Muñoz-Calvo ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Neonatal Diabetes ◽  
Sulfonylurea Receptor ◽  
Sulfonylurea Receptor 1

scholarly journals Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stress

2007 ◽  
Vol 43 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Douglas Stoller ◽  
Rahul Kakkar ◽  
Matthew Smelley ◽  
Karel Chalupsky ◽  
Judy U. Earley ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Sulfonylurea Receptor ◽  
Cardiovascular Stress ◽  
Sulfonylurea Receptor 2
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