Ukr.Biochem.J. 2014; Volume 86, Issue 3, May-Jun, pp. 5-22


ATP-sensitive K(+)-channels in muscle cells: features and physiological role

O. B. Vadzyuk

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

ATP-sensitive K+-channels of plasma membranes belong to the inward rectifier potassium channels type. They are involved in coupling of electrical activity of muscle cell with its metabolic­ state. These channels are heterooctameric and consist of two types of subunits: four poreforming (Kir 6.х) and four regulatory (SUR, sulfonylurea receptor). The Kir subunits contain highly selective K+ filter and provide for high-velocity K+ currents. The SUR subunits contain binding sites for activators and blockers and have metabolic sensor, which enables channel activation under conditions of metabolic stress. ATP blocks K+ currents through the ATP-sensitive K+-channels in the most types of muscle cells. However, functional activity of these channels does not depend on absolute concentration of ATP but on the АТР/ADP ratio and presence of Mg2+. Physiologically active substances, such as phosphatidylinositol bisphosphate and fatty acid esters can regulate the activity of these structures in muscle cells. Activation of these channels under ischemic conditions underlies their cytoprotective action, which results in prevention of Ca2+ overload in cytosol. In contrast to ATP-sensitive K+-channels of plasma membranes, the data regarding the structure and function of ATP-sensitive K+-channels of mitochondrial membrane are contradictory. Pore-forming subunits of this channel have not been firmly identified yet. ATP-sensitive K+ transport through the mitochondrial­ membrane is easily tested by different methods, which are briefly reviewed in this paper.  Interaction of mitoKATP with physiological and pharmacological ligands is discussed as well.

Keywords: , , , , ,


  1. Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M. Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev. 2000 Dec;52(4):557-94. Review. PubMed
  2. MacKinnon R. Potassium channels. FEBS Lett. 2003 Nov 27;555(1):62-5. Review. PubMed, CrossRef
  3. Tamargo J, Caballero R, Gómez R, Valenzuela C, Delpón E. Pharmacology of cardiac potassium channels. Cardiovasc Res. 2004 Apr 1;62(1):9-33. Review. PubMed, CrossRef
  4. Shuba Ia. M. Fundamentals of molecular physiology of ion channels. K.: Nauk. dumka, 2010. 446 p.
  5. Dick GM, Tune JD. Role of potassium channels in coronary vasodilation. Exp Biol Med (Maywood). 2010 Jan;235(1):10-22. Review. PubMed, CrossRef
  6. Amberg GC, Koh SD, Imaizumi Y, Ohya S, Sanders KM. A-type potassium currents in smooth muscle. Am J Physiol Cell Physiol. 2003 Mar;284(3):C583-95. Review. PubMed, CrossRef
  7. Straub SV, Nelson MT. A spoonful of sugar helps the KV channel activity go down. J Physiol. 2006 Sep 15;575(Pt 3):691. PubMed, PubMedCentral, CrossRef
  8. Sobey CG. Potassium channel function in vascular disease. Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):28-38. Review. PubMed, CrossRef
  9. Berkefeld H, Fakler B, Schulte U. Ca2+-activated K+ channels: from protein complexes to function. Physiol Rev. 2010 Oct;90(4):1437-59. Review. PubMed, CrossRef
  10. Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel. J Biol Chem. 2004 Aug 27;279(35):36746-52. PubMed, CrossRef
  11. Brown A, Cornwell T, Korniyenko I, Solodushko V, Bond CT, Adelman JP, Taylor MS. Myometrial expression of small conductance Ca2+-activated K+ channels depresses phasic uterine contraction. Am J Physiol Cell Physiol. 2007 Feb;292(2):C832-40. PubMed, CrossRef
  12. O’Connell AD, Morton MJ, Hunter M. Two-pore domain K+ channels-molecular sensors. Biochim Biophys Acta. 2002 Nov 13;1566(1-2):152-61. Review. PubMed, CrossRef
  13. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010 Jan;90(1):291-366. Review. PubMed, CrossRef
  14. Farzaneh T, Tinker A. Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits. Cardiovasc Res. 2008 Sep 1;79(4):621-31. Epub 2008 Jun 3. PubMed, CrossRef
  15. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8-14;305(5930):147-8. PubMed, CrossRef
  16. Yokoshiki H, Sunagawa M, Seki T, Sperelakis N. ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells. Am J Physiol. 1998 Jan;274(1 Pt 1):C25-37. Review. PubMed
  17. Nielsen JJ, Kristensen M, Hellsten Y, Bangsbo J, Juel C. Localization and function of ATP-sensitive potassium channels in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R558-63. PubMed, CrossRef
  18. Quast U. ATP-sensitive K+ channels in the kidney. Naunyn Schmiedebergs Arch Pharmacol. 1996 Aug-Sep;354(3):213-25. Review. PubMed, CrossRef
  19. Wan E, Kushner JS, Zakharov S, Nui XW, Chudasama N, Kelly C, Waase M, Doshi D, Liu G, Iwata S, Shiomi T, Katchman A, D’Armiento J, Homma S, Marx SO. Reduced vascular smooth muscle BK channel current underlies heart failure-induced vasoconstriction in mice. FASEB J. 2013 May;27(5):1859-67. PubMed, PubMedCentral, CrossRef
  20. Patel AJ, Honoré E. Molecular physiology of oxygen-sensitive potassium channels. Eur Respir J. 2001 Jul;18(1):221-7. Review. PubMed, CrossRef
  21. Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999 Apr;20(2):101-35. Review. PubMed, CrossRef
  22. Teramoto N. Physiological roles of ATP-sensitive K+ channels in smooth muscle. J Physiol. 2006 May 1;572(Pt 3):617-24. Review. PubMed, PubMedCentral, CrossRef
  23. Minami K, Miki T, Kadowaki T, Seino S. Roles of ATP-sensitive K+ channels as metabolic sensors: studies of Kir6.x null mice. Diabetes. 2004 Dec;53 Suppl 3:S176-80. Review. PubMed, CrossRef
  24. Bryan J, Vila-Carriles WH, Zhao G, Babenko AP, Aguilar-Bryan L. Toward linking structure with function in ATP-sensitive K+ channels. Diabetes. 2004 Dec;53 Suppl 3:S104-12. Review. PubMed, CrossRef
  25. Li L, Wang J, Drain P. The I182 region of k(ir)6.2 is closely associated with ligand binding in K(ATP) channel inhibition by ATP. Biophys J. 2000 Aug;79(2):841-52. PubMed, PubMedCentral, CrossRef
  26. Shyng SL, Cukras CA, Harwood J, Nichols CG. Structural determinants of PIP(2) regulation of inward rectifier K(ATP) channels. J Gen Physiol. 2000 Nov;116(5):599-608. PubMed, PubMedCentral, CrossRef
  27. Flagg TP, Enkvetchakul D, Koster JC, Nichols CG. Muscle KATP channels: recent insights to energy sensing and myoprotection. Physiol Rev. 2010 Jul;90(3):799-829. Review. PubMed, PubMedCentral, CrossRef
  28. Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM. Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor. Nature. 1997 May 8;387(6629):179-83. PubMed, CrossRef
  29. Trapp S, Proks P, Tucker SJ, Ashcroft FM. Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP. J Gen Physiol. 1998 Sep;112(3):333-49. PubMed, PubMedCentral, CrossRef
  30. Burke MA, Mutharasan RK, Ardehali H. The sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel. Circ Res. 2008 Feb 1;102(2):164-76. Review. PubMed, CrossRef
  31. Pratt EB, Zhou Q, Gay JW, Shyng SL. Engineered interaction between SUR1 and Kir6.2 that enhances ATP sensitivity in KATP channels. J Gen Physiol. 2012 Aug;140(2):175-87. Epub 2012 Jul 16. PubMed, PubMedCentral, CrossRef
  32. de Wet H, Shimomura K, Aittoniemi J, Ahmad N, Lafond M, Sansom MS, Ashcroft FM. A universally conserved residue in the SUR1 subunit of the KATP channel is essential for translating nucleotide binding at SUR1 into channel opening. J Physiol. 2012 Oct 15;590(Pt 20):5025-36. PubMed, PubMedCentral, CrossRef
  33. Han J, Kim N, Joo H, Kim E, Earm YE. ATP-sensitive K(+) channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol. 2002 Oct;283(4):H1545-54. PubMed, CrossRef
  34. Enkvetchakul D, Nichols CG. Gating mechanism of KATP channels: function fits form. J Gen Physiol. 2003 Nov;122(5):471-80. Review. PubMed, PubMedCentral, CrossRef
  35. Linton KJ. Structure and function of ABC transporters. Physiology (Bethesda). 2007 Apr;22:122-30. Review. PubMed, CrossRef
  36. Chan KW, Zhang H, Logothetis DE. N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits. EMBO J. 2003 Aug 1;22(15):3833-43. PubMed, PubMedCentral, CrossRef
  37. Mikhailov MV, Campbell JD, de Wet H, Shimomura K, Zadek B, Collins RF, Sansom MS, Ford RC, Ashcroft FM. 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1. EMBO J. 2005 Dec 7;24(23):4166-75. PubMed, PubMedCentral, CrossRef
  38. Masia R, Nichols CG. Functional clustering of mutations in the dimer interface of the nucleotide binding folds of the sulfonylurea receptor. J Biol Chem. 2008 Oct 31;283(44):30322-9. PubMed, PubMedCentral, CrossRef
  39. Inagaki N, Gonoi T, Clement JP 4th, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995 Nov 17;270(5239):1166-70. PubMed, CrossRef
  40. Hosy E, Dérand R, Revilloud J, Vivaudou M. Remodelling of the SUR-Kir6.2 interface of the KATP channel upon ATP binding revealed by the conformational blocker rhodamine 123. J Physiol. 2007 Jul 1;582(Pt 1):27-39. PubMedPubMedCentral
  41. Zerangue N, Schwappach B, Jan YN, Jan LY. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron. 1999 Mar;22(3):537-48. PubMed, CrossRef
  42. Conti LR, Radeke CM, Vandenberg CA. Membrane Targeting of ATP-sensitive Potassium Channel. Effects of glycosylation on surface expression. J Biol Chem. 2002;277(28):25416–25422. CrossRef
  43.  Inagaki N, Inazawa J, Seino S. cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Genomics. 1995 Nov 1;30(1):102-4. PubMed, CrossRef
  44. Suzuki M, Li RA, Miki T, Uemura H, Sakamoto N, Ohmoto-Sekine Y, Tamagawa M, Ogura T, Seino S, Marbán E, Nakaya H. Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice. Circ Res. 2001 Mar 30;88(6):570-7. PubMed, CrossRef
  45. Hambrock A, Löffler-Walz C, Kloor D, Delabar U, Horio Y, Kurachi Y, Quast U. ATP-Sensitive K+ channel modulator binding to sulfonylurea receptors SUR2A and SUR2B: opposite effects of MgADP. Mol Pharmacol. 1999 May;55(5):832-40. PubMed
  46. Hambrock A, Kayar T, Stumpp D, Osswald H. Effect of two amino acids in TM17 of Sulfonylurea receptor SUR1 on the binding of ATP-sensitive K+ channel modulators. Diabetes. 2004 Dec;53 Suppl 3:S128-34. PubMed, CrossRef
  47. Karger AB, Park S, Reyes S, Bienengraeber M, Dyer RB, Terzic A, Alekseev AE. Role for SUR2A ED domain in allosteric coupling within the K(ATP) channel complex. J Gen Physiol. 2008 Mar;131(3):185-96. PubMed, PubMedCentral, CrossRef
  48. Yamada M, Kurachi Y. The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K+ channels. Mol Pharmacol. 2004 May;65(5):1198-207. PubMed, CrossRef
  49. Gribble FM, Reimann F, Ashfield R, Ashcroft FM. Nucleotide modulation of pinacidil stimulation of the cloned K(ATP) channel Kir6.2/SUR2A. Mol Pharmacol. 2000 Jun;57(6):1256-61. PubMed
  50. Schwanstecher M, Sieverding C, Dörschner H, Gross I, Aguilar-Bryan L, Schwanstecher C, Bryan J. Potassium channel openers require ATP to bind to and act through sulfonylurea receptors. EMBO J. 1998 Oct 1;17(19):5529-35. PubMed, PubMedCentral, CrossRef
  51. Gribble FM, Tucker SJ, Ashcroft FM. The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide. EMBO J. 1997 Mar 17;16(6):1145-52. PubMed, PubMedCentral, CrossRef
  52. Koster JC, Sha Q, Nichols CG. Sulfonylurea and K(+)-channel opener sensitivity of K(ATP) channels. Functional coupling of Kir6.2 and SUR1 subunits. J Gen Physiol. 1999 Aug;114(2):203-13. PubMed, PubMedCentral, CrossRef
  53. Shimokawa J, Yokoshiki H, Tsutsui H. Impaired activation of ATP-sensitive K+ channels in endocardial myocytes from left ventricular hypertrophy. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3643-9. PubMed, CrossRef
  54. Beech DJ, Zhang H, Nakao K, Bolton TB. K channel activation by nucleotide diphosphates and its inhibition by glibenclamide in vascular smooth muscle cells. Br J Pharmacol. 1993 Oct;110(2):573-82. PubMed, PubMedCentral, CrossRef
  55. Pfründer D, Anghelescu I, Kreye VA. Intracellular ADP activates ATP-sensitive K+ channels in vascular smooth muscle cells of the guinea pig portal vein. Pflugers Arch. 1993 Apr;423(1-2):149-51. PubMed, CrossRef
  56. Terzic A, Findlay I, Hosoya Y, Kurachi Y. Dualistic behavior of ATP-sensitive K+ channels toward intracellular nucleoside diphosphates. Neuron. 1994 May;12(5):1049-58. PubMed, CrossRef
  57. Tung RT, Kurachi Y. On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. J Physiol. 1991 Jun;437:239-56. PubMed, PubMedCentral, CrossRef
  58. Crawford RM, Ranki HJ, Botting CH, Budas GR, Jovanovic A. Creatine kinase is physically associated with the cardiac ATP-sensitive K+ channel in vivo. FASEB J. 2002 Jan;16(1):102-4. PubMed, PubMedCentral
  59. Crawford RM, Budas GR, Jovanović S, Ranki HJ, Wilson TJ, Davies AM, Jovanović A. M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia. EMBO J. 2002 Aug 1;21(15):3936-48. PubMed, PubMedCentral, CrossRef
  60. Carrasco AJ, Dzeja PP, Alekseev AE, Pucar D, Zingman LV, Abraham MR, Hodgson D, Bienengraeber M, Puceat M, Janssen E, Wieringa B, Terzic A. Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels. Proc Natl Acad Sci USA. 2001 Jun 19;98(13):7623-8.  PubMed, PubMedCentral, CrossRef
  61. Yokoshiki H, Katsube Y, Sunugawa M, Seki T, Sperelakis N. Disruption of actin cytoskeleton attenuates sulfonylurea inhibition of cardiac ATP-sensitive K+ channels. Pflugers Arch. 1997 Jun;434(2):203-5. PubMed, CrossRef
  62. Terzic A, Kurachi Y. Actin microfilament disrupters enhance K(ATP) channel opening in patches from guinea-pig cardiomyocytes. J Physiol. 1996 Apr 15;492 ( Pt 2):395-404. PubMed, PubMedCentral, CrossRef
  63. Quinn KV, Giblin JP, Tinker A. Multisite phosphorylation mechanism for protein kinase A activation of the smooth muscle ATP-sensitive K+ channel. Circ Res. 2004 May 28;94(10):1359-66. PubMed, CrossRef
  64. Shi Y, Wu Z, Cui N, Shi W, Yang Y, Zhang X, Rojas A, Ha BT, Jiang C. PKA phosphorylation of SUR2B subunit underscores vascular KATP channel activation by beta-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1205-14. PubMed, PubMedCentral, CrossRef
  65. Cole WC, Malcolm T, Walsh MP, Light PE. Inhibition by protein kinase C of the K(NDP) subtype of vascular smooth muscle ATP-sensitive potassium channel. Circ Res. 2000 Jul 21;87(2):112-7. PubMed, CrossRef
  66. Light PE, Sabir AA, Allen BG, Walsh MP, French RJ. Protein kinase C-induced changes in the stoichiometry of ATP binding activate cardiac ATP-sensitive K+ channels. A possible mechanistic link to ischemic preconditioning. Circ Res. 1996 Sep;79(3):399-406. PubMed, CrossRef
  67. Manning Fox JE, Karaman G, Wheeler MB. Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells. Biochem Biophys Res Commun. 2006 Nov 17;350(2):492-7. PubMed, CrossRef
  68. Proks P, Takano M, Ashcroft FM. Effects of intracellular pH on ATP-sensitive K+ channels in mouse pancreatic beta-cells. J Physiol. 1994 Feb 15;475(1):33-44. PubMed, PubMedCentral, CrossRef
  69. Koyano T, Kakei M, Nakashima H, Yoshinaga M, Matsuoka T, Tanaka H. ATP-regulated K+ channels are modulated by intracellular H+ in guinea-pig ventricular cells. J Physiol. 1993 Apr;463:747-66. PubMed, PubMedCentral, CrossRef
  70. Xu H, Wu J, Cui N, Abdulkadir L, Wang R, Mao J, Giwa LR, Chanchevalap S, Jiang C. Distinct histidine residues control the acid-induced activation and inhibition of the cloned K(ATP) channel. J Biol Chem. 2001 Oct 19;276(42):38690-6. PubMed, CrossRef
  71. Ribalet B, John SA, Xie LH, Weiss JN. Regulation of the ATP-sensitive K channel Kir6.2 by ATP and PIP(2). J Mol Cell Cardiol. 2005 Jul;39(1):71-7. Review. PubMed, CrossRef
  72. Xie LH, John SA, Ribalet B, Weiss JN. Phosphatidylinositol-4,5-bisphosphate (PIP2) regulation of strong inward rectifier Kir2.1 channels: multilevel positive cooperativity. J Physiol. 2008 Apr 1;586(7):1833-48. PubMed, PubMedCentral, CrossRef
  73. Hilgemann DW, Ball R. Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science. 1996 Aug 16;273(5277):956-9. PubMed, CrossRef
  74. Manning Fox JE, Nichols CG, Light PE. Activation of adenosine triphosphate-sensitive potassium channels by acyl coenzyme A esters involves multiple phosphatidylinositol 4,5-bisphosphate-interacting residues. Mol Endocrinol. 2004 Mar;18(3):679-86. PubMed, CrossRef
  75. Kane GC, Liu XK, Yamada S, Olson TM, Terzic A. Cardiac KATP channels in health and disease. J Mol Cell Cardiol. 2005 Jun;38(6):937-43. Review. PubMed, PubMedCentral, CrossRef
  76. Terzic A, Jahangir A, Kurachi Y. Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+ channel-opening drugs. Am J Physiol. 1995 Sep;269(3 Pt 1):C525-45. Review. PubMed
  77. Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ, Yellon DM, Deanfield JE, MacAllister RJ. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007 Sep 18;116(12):1386-95. PubMed, CrossRef
  78. Ogawa K, Ikewaki K, Taniguchi I, Takatsuka H, Mori C, Sasaki H, Okazaki F, Shimizu M, Mochizuki S. Mitiglinide, a novel oral hypoglycemic agent, preserves the cardioprotective effect of ischemic preconditioning in isolated perfused rat hearts. Int Heart J. 2007 May;48(3):337-45. PubMed, CrossRef
  79. Huffmyer J, Raphael J. Physiology and pharmacology of myocardial preconditioning and postconditioning. Semin Cardiothorac Vasc Anesth. 2009 Mar;13(1):5-18. Review. PubMed, CrossRef
  80. Gumina RJ, Pucar D, Bast P, Hodgson DM, Kurtz CE, Dzeja PP, Miki T, Seino S, Terzic A. Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics. Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2106-13. PubMed, CrossRef
  81. Li L, Wu J, Jiang C. Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various tissues in rats. J Membr Biol. 2003 Nov 1;196(1):61-9. PubMed, CrossRef
  82. Brayden JE. Functional roles of KATP channels in vascular smooth muscle. Clin Exp Pharmacol Physiol. 2002 Apr;29(4):312-6. Review. PubMed, CrossRef
  83. Quayle JM, Turner MR, Burrell HE, Kamishima T. Effects of hypoxia, anoxia, and metabolic inhibitors on KATP channels in rat femoral artery myocytes. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H71-80. PubMed, CrossRef
  84. Daut J, Maier-Rudolph W, von Beckerath N, Mehrke G, Günther K, Goedel-Meinen L. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science. 1990 Mar 16;247(4948):1341-4. PubMed, CrossRef
  85. Stoller DA, Fahrenbach JP, Chalupsky K, Tan BH, Aggarwal N, Metcalfe J, Hadhazy M, Shi NQ, Makielski JC, McNally EM. Cardiomyocyte sulfonylurea receptor 2-KATP channel mediates cardioprotection and ST segment elevation. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1100-8. PubMed, PubMedCentral, CrossRef
  86. Miki T, Suzuki M, Shibasaki T, Uemura H, Sato T, Yamaguchi K, Koseki H, Iwanaga T, Nakaya H, Seino S. Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat Med. 2002 May;8(5):466-72. PubMed, CrossRef
  87. Chutkow WA, Pu J, Wheeler MT, Wada T, Makielski JC, Burant CF, McNally EM. Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 K(ATP) channels. J Clin Invest. 2002 Jul;110(2):203-8. PubMed, PubMedCentral, CrossRef
  88. Quayle JM, Nelson MT, Standen NB. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev. 1997 Oct;77(4):1165-232. Review. PubMed
  89. Teramoto N, Zhu HL, Shibata A, Aishima M, Walsh EJ, Nagao M, Cole WC. ATP-sensitive K+ channels in pig urethral smooth muscle cells are heteromultimers of Kir6.1 and Kir6.2. Am J Physiol Renal Physiol. 2009 Jan;296(1):F107-17. Epub 2008 Oct 22. PubMed, CrossRef
  90. Xu C, You X, Gao L, Zhang L, Hu R, Hui N, Olson DM, Ni X. Expression of ATP-sensitive potassium channels in human pregnant myometrium. Reprod Biol Endocrinol. 2011 Mar 21;9:35. PubMed, PubMedCentral, CrossRef
  91. Bonev AD, Nelson MT. ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol. 1993 May;264(5 Pt 1):C1190-200. PubMed
  92. Han J, So I, Kim EY, Earm YE. ATP-sensitive potassium channels are modulated by intracellular lactate in rabbit ventricular myocytes. Pflugers Arch. 1993 Dec;425(5-6):546-8. PubMed, CrossRef
  93. Matar W, Nosek TM, Wong D, Renaud J. Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue. Am J Physiol Cell Physiol. 2000 Feb;278(2):C404-16. PubMed
  94. Halestrap AP, Clarke SJ, Khaliulin I. The role of mitochondria in protection of the heart by preconditioning. Biochim Biophys Acta. 2007 Aug;1767(8):1007-31. Review. PubMed, PubMedCentral, CrossRef
  95. Foster DB, Rucker JJ, Marbán E. Is Kir6.1 a subunit of mitoK(ATP)? Biochem Biophys Res Commun. 2008 Feb 15;366(3):649-56. PubMed, PubMedCentral, CrossRef
  96. Garlid KD, Paucek P, Yarov-Yarovoy V, Sun X, Schindler PA. The mitochondrial KATP channel as a receptor for potassium channel openers. J Biol Chem. 1996 Apr 12;271(15):8796-9. PubMed, CrossRef
  97. Mironova GD, Negoda AE, Marinov BS, Paucek P, Costa AD, Grigoriev SM, Skarga YY, Garlid KD. Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR). J Biol Chem. 2004 Jul 30;279(31):32562-8. PubMed, CrossRef
  98. Paucek P, Mironova G, Mahdi F, Beavis AD, Woldegiorgis G, Garlid KD. Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria. J Biol Chem. 1992 Dec 25;267(36):26062-9. PubMed
  99. Bajgar R, Seetharaman S, Kowaltowski AJ, Garlid KD, Paucek P. Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain. J Biol Chem. 2001 Sep 7;276(36):33369-74. PubMed, CrossRef
  100. Ye B, Kroboth SL, Pu JL, Sims JJ, Aggarwal NT, McNally EM, Makielski JC, Shi NQ. Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicing. Circ Res. 2009 Nov 20;105(11):1083-93. PubMed, PubMedCentral, CrossRef
  101. Szewczyk A, Wójcik G, Lobanov NA, Nałecz MJ. The mitochondrial sulfonylurea receptor: identification and characterization. Biochem Biophys Res Commun. 1997 Jan 23;230(3):611-5. PubMed, CrossRef
  102. Queliconi BB, Wojtovich AP, Nadtochiy SM, Kowaltowski AJ, Brookes PS. Redox regulation of the mitochondrial K(ATP) channel in cardioprotection. Biochim Biophys Acta. 2011 Jul;1813(7):1309-15. PubMed, PubMedCentral, CrossRef
  103. Ardehali H, Chen Z, Ko Y, Mejía-Alvarez R, Marbán E. Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP-sensitive K+ channel activity. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11880-5. Epub 2004 Jul 29. PubMed, PubMedCentral, CrossRef
  104. Kowaltowski AJ, Seetharaman S, Paucek P, Garlid KD. Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria. Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H649-57. PubMed
  105. Wojtovich AP1, Nehrke KW, Brookes PS. The mitochondrial complex II and ATP-sensitive potassium channel interaction: quantitation of the channel in heart mitochondria. Acta Biochim Pol. 2010;57(4):431-4. PubMed, PubMedCentral
  106. Wojtovich AP, Brookes PS. The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channels. Basic Res Cardiol. 2009 Mar;104(2):121-9.  PubMed, PubMedCentral, CrossRef
  107. Garlid KD, Sun X, Paucek P, Woldegiorgis G. Mitochondrial cation transport systems. Methods Enzymol. 1995;260:331-48. PubMed, CrossRef
  108. Adebiyi A, McNally EM, Jaggar JH. Sulfonylurea receptor-dependent and -independent pathways mediate vasodilation induced by ATP-sensitive K+ channel openers. Mol Pharmacol. 2008 Sep;74(3):736-43.  PubMed, PubMedCentral, CrossRef
  109. Yang L, Yu T. Prolonged donor heart preservation with pinacidil: the role of mitochondria and the mitochondrial adenosine triphosphate-sensitive potassium channel. J Thorac Cardiovasc Surg. 2010 Apr;139(4):1057-63. PubMed, CrossRef
  110. Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O’Rourke B. Mitochondrial ROMK channel is a molecular component of mitoK(ATP). Circ Res. 2012 Aug 3;111(4):446-54. PubMed, PubMedCentral, CrossRef
  111. Inoue I, Nagase H, Kishi K, Higuti T. ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature. 1991 Jul 18;352(6332):244-7. PubMed, CrossRef
  112. Rottlaender D., Boengler K., Wolny M., Schwaiger A., Motloch  L. J., Ovize M., Schulz R., Heusch G., Hoppe UC. Glycogen synthase kinase 3β transfers cytoprotective signaling through connexin 43 onto mitochondrial ATP-sensitive K+ channels.   Proc Natl Acad Sci U S A. 2012;109(5):E242–E251.  PubMedPubMedCentral, CrossRef
  113. Garlid KD, Paucek P. Mitochondrial potassium transport: the K(+) cycle. Biochim Biophys Acta. 2003 Sep 30;1606(1-3):23-41. Review. PubMed, CrossRef
  114. Facundo HT, de Paula JG, Kowaltowski AJ. Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production. Free Radic Biol Med. 2007 Apr 1;42(7):1039-48. PubMed, CrossRef
  115. Costa AD, Quinlan CL, Andrukhiv A, West IC, Jabůrek M, Garlid KD. The direct physiological effects of mitoK(ATP) opening on heart mitochondria. Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H406-15. PubMed, CrossRef
  116. Garlid KD, Halestrap AP. The mitochondrial K(ATP) channel–fact or fiction? J Mol Cell Cardiol. 2012 Mar;52(3):578-83. PubMed, PubMedCentral, CrossRef
  117. Vadziuk OB, Kosterin SA.Diazoxide-induced mitochondrial swelling in the rat myometrium as a consequence of the activation of the mitochondrial ATP-sensitive (K+)-channel]. Ukr Biokhim Zhurn. 2008 Sep-Oct;80(5):45-51. Russian. PubMed
  118. Vadziuk OB, Chunikhin OIu, Kosterin SO. Effect of mitochondrial ATP-dependent potassium channel effectors diazoxide and glybenclamide on hydrodynamic diameter and membrane potential of the myometrial mitochondria. Ukr Biokhim Zhurn. 2010 Jul-Aug;82(4):40-7. Ukrainian. PubMed
  119.  Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008 Apr;88(2):581-609. Review. PubMed, PubMedCentral, CrossRef
  120. Simerabet M, Robin E, Aristi I, Adamczyk S, Tavernier B, Vallet B, Bordet R, Lebuffe G. Preconditioning by an in situ administration of hydrogen peroxide: involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia-reperfusion model. Brain Res. 2008 Nov 13;1240:177-84. PubMed, CrossRef
  121. Jabůrek M, Costa AD, Burton JR, Costa CL, Garlid KD. Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K+ channel copurify and coreconstitute to form a functioning signaling module in proteoliposomes. Circ Res. 2006 Oct 13;99(8):878-83. PubMed, CrossRef
  122. Iwai T, Tanonaka K, Koshimizu M, Takeo S. Preservation of mitochondrial function by diazoxide during sustained ischaemia in the rat heart. Br J Pharmacol. 2000 Mar;129(6):1219-27. PubMed, PubMedCentral, CrossRef
  123. Aggarwal NT, Pravdic D, McNally EM, Bosnjak ZJ, Shi NQ, Makielski JC. The mitochondrial bioenergetic phenotype for protection from cardiac ischemia in SUR2 mutant mice. Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H1884-90. PubMed, PubMedCentral, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.