© 2000 American Heart Association, Inc.
Editorials |
Mitochondrial KATP Channels
Triggers or Distal Effectors of Ischemic or Pharmacological Preconditioning?
From the Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wis.
Correspondence to Garrett J. Gross, PhD, Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail ggross@mcw.edu
Key Words: mitochondria • KATP channels • diazoxide • preconditioning
 |
Introduction |
|---|
The ATP-sensitive potassium (KATP) channel has been shown by numerous investigations in whole animals, isolated hearts, and cardiac myocytes to be an important downstream mediator of ischemic preconditioning (IPC) or pharmacological preconditioning (PPC). However, in the present issue of Circulation Research, Pain et al1 provide intriguing evidence suggesting that the KATP channel may not be the end effector of IPC or PPC. These authors suggest instead that the KATP channel, specifically the mitochondrial KATP channel, may function as a trigger that sets the myocardium into a preconditioned state via the generation of oxygen-derived free radicals.
Pain et al1 demonstrate in an isolated buffer-perfused
rabbit heart that IPC or the KATP channel openers
pinacidil or diazoxide induce a reduction in infarct size (IS).
5-Hydroxydecanoate (5-HD), a mitochondrial selective
KATP antagonist, and glibenclamide, a
nonselective KATP channel blocker, were included
in the buffer during an early or late protocol to additionally
establish a role for the KATP channel. The early
protocol included the antagonists in the buffer 5 minutes
before, throughout, and 5 minutes after the preconditioning stimulus.
The late protocol, however, included the antagonists in the
perfusate only after the preconditioning stimulus, 5 minutes
before, and throughout the prolonged ischemic insult. These
investigators demonstrate that 5-HD and glibenclamide antagonize
protection only when included during the early protocol, suggesting
that the KATP channel is actually setting the
heart into a preconditioned state. In the same laboratory, Baines et
al2 demonstrated that diazoxide, a mitochondrial
KATP opener, protected the intact rabbit
This article has been cited by other articles:
 |
|
 |
|
  J. A. Segreti, K. C. Marsh, J. S. Polakowski, and R. M. Fryer Evoked Changes in Cardiovascular Function in Rats by Infusion of Levosimendan, OR-1896 [(R)-N-(4-(4-Methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], Dobutamine, and Milrinone: Comparative Effects on Peripheral Resistance, Cardiac Output, dP/dt, Pulse Rate, and Blood Pressure J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Jiang, Y. Nakae, M. Ljubkovic, W.-M. Kwok, D. F. Stowe, and Z. J. Bosnjak Isoflurane Activates Human Cardiac Mitochondrial Adenosine Triphosphate-Sensitive K+ Channels Reconstituted in Lipid Bilayers Anesth. Analg., October 1, 2007; 105(4): 926 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Pagel Levosimendan in Cardiac Surgery: A Unique Drug for the Treatment of Perioperative Left Ventricular Dysfunction or Just Another Inodilator Searching for a Clinical Application? Anesth. Analg., April 1, 2007; 104(4): 759 - 761. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Martin, R. Schulz, H. Post, K. Boengler, M. Kelm, P. Kleinbongard, P. Gres, A. Skyschally, I. Konietzka, and G. Heusch Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia Cardiovasc Res, April 1, 2007; 74(1): 46 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Jiang, M. Ljubkovic, Y. Nakae, Y. Shi, W.-M. Kwok, D. F. Stowe, and Z. J. Bosnjak Characterization of human cardiac mitochondrial ATP-sensitive potassium channel and its regulation by phorbol ester in vitro Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1770 - H1776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Zhao and J. Vinten-Johansen Postconditioning: Reduction of reperfusion-induced injury Cardiovasc Res, May 1, 2006; 70(2): 200 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. O'Rourke Evidence for Mitochondrial K+ Channels and Their Role in Cardioprotection Circ. Res., March 5, 2004; 94(4): 420 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ichinose, H. Yonemochi, T. Sato, and T. Saikawa Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2235 - H2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Digerness, P. S. Brookes, S. P. Goldberg, C. R. Katholi, and W. L. Holman Modulation of mitochondrial adenosine triphosphate-sensitive potassium channels and sodium-hydrogen exchange provide additive protection from severe ischemia-reperfusion injury J. Thorac. Cardiovasc. Surg., April 1, 2003; 125(4): 863 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Akao, B. O'Rourke, H. Kusuoka, Y. Teshima, S. P. Jones, and E. Marban Differential Actions of Cardioprotective Agents on the Mitochondrial Death Pathway Circ. Res., February 7, 2003; 92(2): 195 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H H Lim, S. A Javadov, M. Das, S. J Clarke, M-S. Suleiman, and A. P Halestrap The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration J. Physiol., December 15, 2002; 545(3): 961 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. M Smith, N. Suleman, J. McCarthy, and M. N Sack Classic ischemic but not pharmacologic preconditioning is abrogated following genetic ablation of the TNF{alpha} gene Cardiovasc Res, August 15, 2002; 55(3): 553 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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. [Full Text] [PDF]
|
|
|
|
|
|
H. H. Patel and G. J. Gross Diazoxide induced cardioprotection: what comes first, KATP channels or reactive oxygen species? Cardiovasc Res, September 1, 2001; 51(4): 633 - 636. [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu and B. O'Rourke Opening of Mitochondrial KATP Channels Triggers Cardioprotection : Are Reactive Oxygen Species Involved? Circ. Res., April 27, 2001; 88(8): 750 - 752. [Full Text] [PDF]
|
|
|
|
|
|
J. R. Kersten, M. W. Montgomery, T. Ghassemi, E. R. Gross, W. G. Toller, P. S. Pagel, and D. C. Warltier Diabetes and hyperglycemia impair activation of mitochondrial KATP channels Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1744 - H1750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O'Rourke Myocardial KATP Channels in Preconditioning Circ. Res., November 10, 2000; 87(10): 845 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. X. Zhang, Y.-F. Chen, W. B. Campbell, A.-P. Zou, G. J. Gross, and P.-L. Li Characteristics and Superoxide-Induced Activation of Reconstituted Myocardial Mitochondrial ATP-Sensitive Potassium Channels Circ. Res., December 7, 2001; 89(12): 1177 - 1183. [Abstract] [Full Text] [PDF]
|
|