- Sulfonylurea receptor
Name=ATP-binding cassette, sub-family C (CFTR/MRP), member 8
Name=ATP-binding cassette, sub-family C (CFTR/MRP), member 9
In the field of
molecular biology, the sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylureaclass of antidiabeticdrugs whose mechanism of action is to promote insulinrelease from pancreatic beta cells. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channels Kir6.x.cite journal |author=Campbell JD, Sansom MS, Ashcroft FM|title=Potassium channel regulation|journal= EMBO Rep |volume= 4 |issue= 11 |pages= 1038–42 |year= 2003 |pmid= 14593442| doi = 10.1038/sj.embor.7400003] The association of four Kir6.x and four SUR subunits form an ion conducting channel commonly referred to as the KATP channel.
There are three forms of the sulfonylurea receptor, SUR1encoded by the Gene|ABCC8 gene and SUR2A and SUR2B which are splice variants arising from a single Gene|ABCC9 gene.cite journal |author=Aguilar-Bryan L, Clement JP 4th, Gonzalez G, Kunjilwar K, Babenko A, Bryan J|title=Toward understanding the assembly and structure of KATP channels|journal= Physiol Rev |volume= 78 |issue= 1 |pages= 227–45 |year= 1998| url = http://physrev.physiology.org/cgi/content/abstract/78/1/227 |pmid= 9457174]
The primary function of the sulfonylurea receptor is to sense intracellular levels of the
nucleotides ATP and ADP and in response facilitate the open or closing its associated Kir6.x potassium channel. Hence the KATP channel monitors the energy balance within the cell.cite journal |author=Nichols CG|title=KATP channels as molecular sensors of cellular metabolism|journal= Nature |volume= 440 |issue= 7083 |pages= 470–6 |year= 2006| doi = 10.1038/nature04711 |pmid= 16554807]
Depending on the tissue in which the KATP channel is expressed, altering the membrane potential can trigger a variety of down stream events. For example, in pancreatic
beta cells, high levels of glucose lead to increased production of ATP which in turn binds to the KATP channel resulting in channel closure. The reduction in membrane potential in turn opens voltage-dependent calcium channels increasing intracellular calcium concentrations which triggers exocytosisof insulin.
The isoforms of the sulfonylurea receptor have the following tissue distribution:
adipose tissue- SUR2B/Kir6.1
beta cells - SUR1/Kir6.2
cardiac myocytes- SUR2A
skeletal muscle- SUR2A
smooth muscle- SUB2B
The SUR1 protein is coded by the ABCC8 gene and is associated with
congenital hyperinsulinismcite journal |author=Fournet JC, Junien C|title=Genetics of congenital hyperinsulinism|journal= Endocr Pathol |volume= 15 |issue= 3 |pages= 233–40 |year= 2004 |pmid= 15640549|doi=10.1385/EP:15:3:233] and susceptibility to type 2 diabetes.cite journal |author=Reis AF, Velho G|title=Sulfonylurea receptor -1 (SUR1): genetic and metabolic evidences for a role in the susceptibility to type 2 diabetes mellitus|journal= Diabetes Metab |volume= 28 |issue= 1 |pages= 14–9 |year= 2002 |pmid= 11938023]
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