The Journal of Thoracic and Cardiovascular Surgery
Volume 140, Issue 5 , Pages 1153-1159 , November 2010

Diazoxide maintenance of myocyte volume and contractility during stress: Evidence for a non-sarcolemmal KATP channel location

Read at the 90th Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, May 1–5, 2010.

  • Angela D. Sellitto, MS

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo
  • ,
  • Sara K. Maffit, BS

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo
  • ,
  • Ashraf S. Al-Dadah, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo
  • ,
  • Haixia Zhang, PhD

      Affiliations

    • Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Mo
  • ,
  • Richard B. Schuessler, PhD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo
  • ,
  • Colin G. Nichols, PhD

      Affiliations

    • Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Mo
  • ,
  • Jennifer S. Lawton, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo
    • Corresponding Author InformationAddress for reprints: Jennifer S. Lawton, MD, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8234, St Louis, MO 63110.

Received 28 April 2010 ,Revised 12 July 2010 ,Accepted 16 July 2010.

References 

  1. Liu Y, Sato T, O'Rourke B, Marban E. Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?. Circulation. 1998;97:2463–2470
  2. Mizutani S, Al-Dadah AS, Bloch JB, Prasad SM, Diodato MD, Schuessler RB, et al. Hyperkalemic cardioplegia-induced myocyte swelling and contractile dysfunction: prevention by diazoxide. Ann Thorac Surg. 2006;81:154–159
  3. Prasad SM, Al-Dadah AS, Byrd GD, Flagg TP, Gomes J, Damiano RJ, et al. Role of the sarcolemmal adenosine triphosphate-sensitive potassium channel in hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility. Ann Thorac Surg. 2006;81:148–153
  4. Al-Dadah AS, Voeller RK, Schuessler RB, Damiano RJ, Lawton JS. Maintenance of myocyte volume homeostasis during stress by diazoxide is cardioprotective. Ann Thorac Surg. 2007;84:857–862
  5. Mizutani S, Prasad SM, Sellitto AD, Schuessler RB, Damiano RJ, Lawton JS. Myocyte volume and function in response to osmotic stress: observations in the presence of an adenosine triphosphate-sensitive potassium channel opener. Circulation. 2005;112(9 Suppl):I219–I223
  6. Hu H, Sato T, Seharaseyon J, Liu Y, Johns DC, O'Rourke B, et al. Pharmacological and histological distinctions between molecularly defined sarcolemmal KATP channels and native cardiac mitochondrial KATP channels. Mol Pharm. 1999;55:1000–1005
  7. Das M, Parker JE, Halestrap AP. Matrix volume measurements challenge the existence of diazoxide/glibenclamide-sensitive KATP channels in rat mitochondria. J Physiol. 2003;547:893–902
  8. D'hahan N, Moreau C, Prost AL, Jacquet H, Alekseev AE, Terzic A. Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc Natl Acad Sci. 1999;96:12162–12167
  9. Grover GJ, Garlid KD. ATP-sensitive potassium channels: a review of their cardioprotective pharmacology. J Mol Cell Cardiol. 2000;32:677–695
  10. Shyng S-L, Nichols CG. Octameric stoichiometry of the KATP channel complex. J Gen Physiol. 1997;110:655–664
  11. Flagg TP, Kurata HT, Masia R, Caputa G, Magnuson MA, Lefer DJ, et al. Differential structure of atrial and ventricular KATP: atrial KATP channels require SUR1. Circ Res. 2008;103:1458–1465
  12. Elrod JW, Harrell M, Flagg TP, Gundewar S, Magnuson MA, Nichols CG, et al. Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury. Circulation. 2008;117:1405–1413
  13. Yokoshiki H, Sunagawa M. Antisense oligonucleotides of sulfonylurea receptors inhibit ATP-sensitive K+ channels in cultured neonatal rat ventricular cells. Pflugers Arch. 1999;437:400–408
  14. Flagg TP, Remedi MS, Masia R, Gomes J, McLerie M, Lopatin A, et al. Transgenic overexpression of SUR1 in the heart suppresses sarcolemmal KATP. J Mol Cell Cardiol. 2005;39:647–656
  15. Drewnowska K, Clemo HF, Baumgarten CM. Prevention of myocardial intracellular edema induced by St. Thomas' hospital cardioplegic solution. J Mol Cell Cardiol. 1991;23:1215–1221
  16. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981;391:85–100
  17. Flagg TP, Charpentier F, Manning-Fox J, Remedi MS, Enkvetchakul D, Lopatin A, et al. Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels. Am J Physiol Heart Circ Physiol. 2004;286:H1361–H1369
  18. Shiota C, Larsson O, Shelton KD, Shiota M, Efanov AM, Hoy M, et al. Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. J Biol Chem. 2002;277:37176–37183
  19. Garlid KD, Paucek P, Yarov-Yarovoy V, Murray HN, Darbenzio RB, D'Alonzo AJ. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K channels: possible mechanism of cardioprotection. Circ Res. 1997;81:1072–1082
  20. Nichols CG. KATP channels as molecular sensors of cellular metabolism. Nature. 2006;440:470–476
  21. Chutkow WA, Pu J, Wheeler MT, Wada T, Makielski JC, Burant CF, et al. Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 K(ATP) channels. J Clin Invest. 2002;110:203–208
  22. Arena JP, Kass RS. Enhancement in potassium-sensitive current in heart cells by pinacidil: Evidence for the modulation of the ATP-sensitive potassium channel. Circ Res. 1989;65:436–445
  23. Nichols CG, Ripol C, Lederer WJ. ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction. Circ Res. 1991;68:280–287
  24. Toyoda Y, Levitsky S, McCully JD. Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection. Ann Thorac Surg. 2001;71:1281–1288
  25. Sato T, Sasaki N, Seharaseyon J, O'Rourke B, Marban E. Selective pharmacological agents implicate mitochondrial but not sarcolemmal KATP channels in ischemic cardioprotection. Circulation. 2000;101:2418–2423
  26. Hanley PJ, Mickel M, Loffler M, Brandt U, Daut J. KATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart. J Physiol. 2002;542.3:735-41
  27. Lim KH, Javadov SA, Das M, Clarke SJ, Suleiman M, Halestrap AP. The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration. J Physiol. 2002;545.3:961-74
  28. Rainbow RD, Lodwick D, Hudman D, Davies NW, Norman RI, Standen NB. SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes. J Physiol. 2004;557.3:785-94
  29. Sorgato MC, Keller BU, Stuhmer W. Patch-clamping of the inner mitochondrial membrane reveals a voltage-dependent ion channel. Nature. 1987;330:498–500
  30. Soltysinska E, Olesen SP, Christ T, Wetter E, Varro A, Grunnet M, et al. Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts. Pflugers Arch. 2009;459:11–23

 Supported by the American Heart Association Beginning Grant in Aid 0565514Z (JSL) and the Thoracic Surgery Foundation for Research and Education Nina Starr Braunwald Career Development Award (JSL).

 Disclosures: None.

PII: S0022-5223(10)00772-5

doi: 10.1016/j.jtcvs.2010.07.047

The Journal of Thoracic and Cardiovascular Surgery
Volume 140, Issue 5 , Pages 1153-1159 , November 2010