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Circulation Research. 1999;84:973-979

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(Circulation Research. 1999;84:973-979.)
© 1999 American Heart Association, Inc.


Mini Review

Sarcolemmal Versus Mitochondrial ATP-Sensitive K+ Channels and Myocardial Preconditioning

Garrett J. Gross, Ryan M. Fryer

From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis.

Correspondence to Garrett J. Gross, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI. E-mail ggross{at}post.its.mcw.edu

Abstract

Abstract—Ischemic preconditioning (IPC) is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the heart against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of stunning, or incidence of cardiac arrhythmias. Although a number of substances and signaling pathways have been proposed to be involved in mediating the cardioprotective effect of IPC, the overwhelming majority of evidence suggests that the ATP-sensitive potassium channel (KATP channel) is an important component of this phenomenon and may serve as the end effector in this process. Initially, it was hypothesized that the surface or sarcolemmal KATP (sarc KATP) channel mediated protection observed after IPC; however, subsequent evidence suggested that the recently identified mitochondrial KATP channel (mito KATP) may be the potassium channel mediating IPC-induced cardioprotection. In this review, evidence will be presented supporting a role for either the sarc KATP or the mito KATP in IPC and potential mechanisms by which opening these channels may produce cardioprotection; additionally, we will address important questions that still need to be investigated to define the role of the sarc or mito KATP channel, or both, in cardiac pathophysiology.


Key Words: ischemic preconditioning • ATP-sensitive K+ channel • mitochondria • sarcolemma




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CirculationHome page
K.M. Lawrence, A. Chanalaris, T. Scarabelli, M. Hubank, E. Pasini, P.A. Townsend, L. Comini, R. Ferrari, A. Tinker, A. Stephanou, et al.
KATP Channel Gene Expression Is Induced by Urocortin and Mediates Its Cardioprotective Effect
Circulation, September 17, 2002; 106(12): 1556 - 1562.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
R. Ockaili, F. Salloum, J. Hawkins, and R. C. Kukreja
Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits
Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1263 - H1269.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
K. Shimizu, Z. Lacza, N. Rajapakse, T. Horiguchi, J. Snipes, and D. W. Busija
MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat
Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1005 - H1011.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
O. Oldenburg, M. V Cohen, D. M Yellon, and J. M Downey
Mitochondrial KATP channels: role in cardioprotection
Cardiovasc Res, August 15, 2002; 55(3): 429 - 437.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
Z.-Q. Zhao and J. Vinten-Johansen
Myocardial apoptosis and ischemic preconditioning
Cardiovasc Res, August 15, 2002; 55(3): 438 - 455.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
D. Garcia-Dorado, M. Ruiz-Meana, F. Padilla, A. Rodriguez-Sinovas, and M. Mirabet
Gap junction-mediated intercellular communication in ischemic preconditioning
Cardiovasc Res, August 15, 2002; 55(3): 456 - 465.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
G.F Baxter
Role of adenosine in delayed preconditioning of myocardium
Cardiovasc Res, August 15, 2002; 55(3): 483 - 494.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
Y.-P. Wang, H. Maeta, K. Mizoguchi, T. Suzuki, Y. Yamashita, and M. Oe
Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial KATP channel
Cardiovasc Res, August 15, 2002; 55(3): 576 - 582.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
H. F del Valle, E. C Lascano, and J. A Negroni
Ischemic preconditioning protection against stunning in conscious diabetic sheep: role of glucose, insulin, sarcolemmal and mitochondrial KATP channels
Cardiovasc Res, August 15, 2002; 55(3): 642 - 659.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
N B Standen
Cardioprotection by preconditioning: KATP channels, metabolism, or both?
J. Physiol., August 1, 2002; 542(3): 666 - 666.
[Full Text] [PDF]


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J. Physiol.Home page
P. J Hanley, M. Mickel, M. Loffler, U. Brandt, and J. Daut
KATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart
J. Physiol., August 1, 2002; 542(3): 735 - 741.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
R. Rajashree, J. C. Koster, K. P. Markova, C. G. Nichols, and P. A. Hofmann
Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal KATP channels
Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H584 - H590.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
H. J. Ranki, G. R. Budas, R. M. Crawford, A. M. Davies, and A. Jovanovic
17{beta}-Estradiol regulates expression of KATP channels in heart-derived H9c2 cells
J. Am. Coll. Cardiol., July 17, 2002; 40(2): 367 - 374.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
Z. Ren, Q. Yang, H. Storm Floten, and G.-W. He
Hypoxic preconditioning in coronary microarteries: role of EDHF and K+ channel openers
Ann. Thorac. Surg., July 1, 2002; 74(1): 143 - 148.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
J. Han, N. Kim, H. Joo, and E. Kim
Ketamine abolishes ischemic preconditioning through inhibition of KATP channels in rabbit hearts
Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H13 - H21.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
E. W. Dickson, R. J. Tubbs, W. A. Porcaro, W. J. Lee, D. J. Blehar, R. E. Carraway, C. E. Darling, and K. Przyklenk
Myocardial preconditioning factors evoke mesenteric ischemic tolerance via opioid receptors and KATP channels
Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H22 - H28.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
D. A. Liem, P. D. Verdouw, H. Ploeg, S. Kazim, and D. J. Duncker
Sites of action of adenosine in interorgan preconditioning of the heart
Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H29 - H37.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
M. Tonkovic-Capin, G. J. Gross, Z. J. Bosnjak, J. S. Tweddell, C. M. Fitzpatrick, and J. E. Baker
Delayed cardioprotection by isoflurane: role of KATP channels
Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H61 - H68.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
P. Dos Santos, A. J. Kowaltowski, M. N. Laclau, S. Seetharaman, P. Paucek, S. Boudina, J.-B. Thambo, L. Tariosse, and K. D. Garlid
Mechanisms by which opening the mitochondrial ATP- sensitive K+ channel protects the ischemic heart
Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H284 - H295.
[Abstract] [Full Text] [PDF]


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J. Exp. Biol.Home page
T. J. MacCormack and W. R. Driedzic
Mitochondrial ATP-sensitive K+ channels influence force development and anoxic contractility in a flatfish, yellowtail flounder Limanda ferruginea, but not Atlantic cod Gadus morhua heart
J. Exp. Biol., May 15, 2002; 205(10): 1411 - 1418.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
H. Liu, H. Y. Zhang, X. Zhu, Z. Shao, and Z. Yao
Preconditioning blocks cardiocyte apoptosis: role of KATP channels and PKC-epsilon
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1380 - H1386.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
B. Pouzet, J.-B. Lecharny, M. Dehoux, S. Paquin, M. Kitakaze, J. Mantz, and P. Menasche
Is there a place for preconditioning during cardiac operations in humans?
Ann. Thorac. Surg., March 1, 2002; 73(3): 843 - 848.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
P. Korge, H. M. Honda, and J. N. Weiss
Protection of cardiac mitochondria by diazoxide and protein kinase C: Implications for ischemic preconditioning
PNAS, February 20, 2002; (2002) 52713199.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
D.V. Cokkinos
Can metabolic manipulation reverse myocardial dysfunction?
Eur. Heart J., December 1, 2001; 22(23): 2138 - 2139.
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FASEB J.Home page
P. E. LIGHT, H. D. KANJI, J. E. M. FOX, and R. J. FRENCH
Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial KATP channels during metabolic inhibition and recovery
FASEB J, December 1, 2001; 15(14): 2586 - 2594.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch
Signal transduction of ischemic preconditioning
Cardiovasc Res, November 1, 2001; 52(2): 181 - 198.
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J. Appl. Physiol.Home page
K. N. Jew and R. L. Moore
Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats
J Appl Physiol, October 1, 2001; 91(4): 1545 - 1554.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
J. An, S. G. Varadarajan, E. Novalija, and D. F. Stowe
Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+ responses in intact hearts
Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1508 - H1523.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
K. Mubagwa and W. Flameng
Adenosine, adenosine receptors and myocardial protection: An updated overview
Cardiovasc Res, October 1, 2001; 52(1): 25 - 39.
[Abstract] [Full Text] [PDF]