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ATP-binding cassette, subfamily C (CFTR/MRP), member 9
ATP-binding cassette, subfamily C (CFTR/MRP), member 9
Identifiers
Symbol	ABCC9
Alt. symbols	SUR2A, SUR2B
NCBI gene	10060
HGNC	60
OMIM	601439
RefSeq	NM_005691
UniProt	O60706
Other data
Locus	Chr. 12 p12.1
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

ATP-binding cassette, subfamily C (CFTR/MRP), member 8
ATP-binding cassette, subfamily C (CFTR/MRP), member 8
Identifiers
Symbol	ABCC8
Alt. symbols	SUR1
NCBI gene	6833
HGNC	59
OMIM	600509
RefSeq	NM_000352
UniProt	Q09428
Other data
Locus	Chr. 11 p15.1
Structures
Search for
Structures	Swiss-model
Domains	InterPro

In molecular biology, the sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of antidiabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channels K_ir6.x (6.1 and 6.2).^[1] The association of four K_ir6.x and four SUR subunits form an ion conducting channel commonly referred to as the K_ATP channel.^[2]

Three forms of the sulfonylurea receptor are known, SUR1 encoded by the ABCC8 gene, and SUR2A and SUR2B, which are splice variants arising from a single ABCC9 gene.^[3]

Function

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 K_ir6.x potassium channel. Hence, the K_ATP channel monitors the energy balance within the cell.^[4]

Depending on the tissue in which the K_ATP channel is expressed, altering the membrane potential can trigger a variety of downstream events. For example, in pancreatic beta cells, high levels of glucose lead to increased production of ATP, which, in turn, binds to the K_ATP channel resulting in channel closure. The relative depolarization (decrease in membrane hyperpolarization), in turn, opens voltage-dependent calcium channels increasing intracellular calcium concentrations, which triggers exocytosis of insulin.

Under cerebral ischemic conditions, SUR1, the regulatory subunit of the K_ATP and the NC_Ca-ATP channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells^[5] and by reactive microglia.^[6] Blockade of SUR1 receptors with glibenclamide has been involved in improved outcome in animal stroke models and investigational human studies by preventing brain swelling^[7] and enhancing neuroprotection.^[6]

Tissue distribution

The isoforms of the sulfonylurea receptor have the following tissue distribution:

Adipose tissue - SUR2B/K_ir6.1
Pancreatic beta cells - SUR1/K_ir6.2
Cardiac myocytes - SUR2A
Skeletal muscle - SUR2A
Smooth muscle - SUR2B
Brain - SUR1, SUR2A and SUR2B ^[5]^[6]

Disease linkage

The SUR1 protein is coded by the ABCC8 gene and is associated with congenital hyperinsulinism^[8] and susceptibility to type 2 diabetes.^[9]

References

^ Campbell JD, Sansom MS, Ashcroft FM (November 2003). "Potassium channel regulation". EMBO Reports. 4 (11): 1038–42. doi:10.1038/sj.embor.embor7400003. PMC 1326373. PMID 14593442.
^ sulfonylurea+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
^ Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J (January 1998). "Toward understanding the assembly and structure of KATP channels". Physiological Reviews. 78 (1): 227–45. doi:10.1152/physrev.1998.78.1.227. PMID 9457174. S2CID 11851627.
^ Nichols CG (March 2006). "KATP channels as molecular sensors of cellular metabolism". Nature. 440 (7083): 470–6. Bibcode:2006Natur.440..470N. doi:10.1038/nature04711. PMID 16554807. S2CID 11899176.
^ ^a ^b Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V (September 2012). "Sulfonylurea receptor 1 in central nervous system injury: a focused review". Journal of Cerebral Blood Flow and Metabolism. 32 (9): 1699–717. doi:10.1038/jcbfm.2012.91. PMC 3434627. PMID 22714048.
^ ^a ^b ^c Ortega FJ, Gimeno-Bayon J, Espinosa-Parrilla JF, Carrasco JL, Batlle M, Pugliese M, Mahy N, Rodríguez MJ (May 2012). "ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats". Experimental Neurology. 235 (1): 282–96. doi:10.1016/j.expneurol.2012.02.010. hdl:2445/34278. PMID 22387180. S2CID 4828181.
^ Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V (April 2006). "Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke". Nature Medicine. 12 (4): 433–40. doi:10.1038/nm1390. PMC 2740734. PMID 16550187.
^ Fournet JC, Junien C (2004). "Genetics of congenital hyperinsulinism". Endocrine Pathology. 15 (3): 233–40. doi:10.1385/EP:15:3:233. PMID 15640549. S2CID 24997856.
^ Reis AF, Velho G (February 2002). "Sulfonylurea receptor -1 (SUR1): genetic and metabolic evidences for a role in the susceptibility to type 2 diabetes mellitus". Diabetes & Metabolism. 28 (1): 14–9. PMID 11938023.