Kir6.2 channels

Channel name Kir6.2
Description ATP-sensitive potassium channel Kir6.2 subunit
Other names BIR
Molecular information Human (KCNJ11): 390aa, Locus ID: 3767, GenBank: NM_000525, chr. 11p15.1
Rat (Kcnj11): 390aa, Locus ID: 83535, GenBank: D86039, NM_031358, PMID: 8798681,1 chr. 1q22
Mouse (Kcnj11): 390aa, Locus ID: 16514, GenBank: D50581, NM_010602, PMID: 7502040,2 8549751,3 chr. 7B3, 7, 41.0 centimorgans
Associated subunits SUR1, SUR2A, and SUR2B in native tissues
Functional assays Voltage-clamp
Current IK(ATP)
Conductance 65 to 80pS (in 140 mM K+)
Ion selectivity K+
Activation MgADP
Inactivation ATP
Activators MgADP, diazoxide, pinacidil, cromokalim, nicorandil (for associated SUR subunits)
Gating inhibitors ATP
Blockers Sulfonylureas, benzamide derivatives, glinides (for associated SUR subunits)
Radioligands [3H]glibenclamides, [125I]iodoglibenclamides (for associated SUR subunits)
Channel distribution Pancreatic β-cell, heart, skeletal muscle, brain
Physiological functions Regulation of insulin secretion in pancreatic β-cells,4 oxygen and glucose sensor in brain,5 cytoprotection during cardiac and brain ischemia,6,7 glucose uptake in skeletal muscle and adipose tissue8
Mutations and pathophysiology Mutations of Kir6.2 or SUR1 are implicated in PHHI of infancy9; mutations of SUR1 and Kir6.2 are implicated in a certain form of diabetes10
Pharmacological significance Kir6.2 is a target for the KATP channel blocker phentolamine; SUR1 is a target for both sulfonylureas and benzamide derivatives used in the treatment of diabetes and diazoxide in the treatment of PHHI
  • aa, amino acids; chr., chromosome; SUR, sulfonylurea receptor; PHHI, persistent hyperinsulinemic hypoglycemia.

  • 1. Isomoto S, Kondo C, Yamada M, Matsumoto S, Higashiguchi O, Horio Y, Matsuzawa Y, and Kurachi Y (1996) A novel sulphonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel. J Biol Chem 271:24321-24324

  • 2. Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, and Bryan J (1995) Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270:1166-1170

  • 3. Sakura H, Ammala C, Smith PA, Gribble FM, and Ashcroft, FM (1995) Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta cells brain heart and skeletal muscle. FEBS Lett 377:338-344

  • 4. Miki T, Nagashima K, Tashiro F, Kotake K, Yoshitomi H, Tamamoto A, Gonoi T, Iwanaga T, Miyazaki J, and Seino S (1998) Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci USA 95:10402-10406

  • 5. Miki T, Liss B, Minami K, Shiuchi T, Saraya A, Kashima Y, Horiuchi M, Ashcroft F, Minokoshi Y, Roeper J, and Seino S. (2001) ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci 4:507-512

  • 6. Suzuki M, Sasaki N, Miki T, Sakamoto N, Ohmoto-Sekine Y, Tamagawa M, Seino S, Marbán E, and Nakaya H (2002) Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice. J Clin Invest 109:509-516

  • 7. Yamada K, Ji JJ, Yuan H, Miki T, Sato S, Horimoto N, Shimizu T, Seino S, and Inagaki N (2001) Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science 292:1543-1546

  • 8. Miki T, Minami K, Zhang L, Morita M, Gonoi T, Shiuchi T, Minokoshi Y, Renaud J-M, and Seino S (2002) ATP-sensitive potassium channels participate in glucose uptake in skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 283:1178-1184

  • 9. Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, Landau H, Stanley CA, Thornton PS, et al. (1997) A nonsense mutation in the inward rectifier potassium channel gene Kir6.2 is associated with familial hyperinsulinism. Diabetes 46:1743-1748

  • 10. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, et al. (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 350:1838–1849 [Erratum in N Engl J Med (2004) 351:1470]