Protein Kinase C and Adenosine Synergistically Activate ATP-Sensitive Potassium Currents: Implications for Ischemic Preconditioning

  • Yongge Liu
  • Wei Dong Gao
  • Brian O’Rourke
  • Eduardo Marban
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 194)


Several mechanisms have been proposed for the mechanism of ischemic preconditioning. Substantial evidence from studies involving rabbit hearts has shown that adenosine receptors, protein kinase C (PKC), and ATP-sensitive potassium (KATP) channels are involved.1’2 Furthermore, it has been suggested that these three hypotheses may be interrelated, with the KATP channel as the final effector.2 Opening of KATP channels shortens the action potential duration (APD). APD abbreviation reduces Ca2+ influx and contractility and thus conserves energy. If opening of KATP channels is the cause of the protection, the activity of KATP channels would need to be increased or primed by the initial preconditioning insult so that they would open more rapidly or to a greater extent during the subsequent ischemia. One explicit scheme2 proposes that adenosine receptor activation stimulates PKC during preconditioning; PKC then phosphorylates KATP channels and the phosphorylation makes the channel open more readily during the second ischemia. The protective effect of adenosine has been linked to KATP channel opening: The protection induced by preconditioning, adenosine receptor agonists and PKC activators can be eliminated by KATP channel blockers.2’3 Likewise, protection from preconditioning and adenosine receptor agonists can be blocked by PKC inhibitors.3 The present chapter summarizes our results examining the effect ofPKC and adenosine on KATPchannels in heart cells. The reader is referred to the full-length paper4 for details.


Adenosine Receptor KATP Channel Ischemic Precondition Action Potential Duration Metabolic Inhibition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Downey JM, Cohen MV, Ytrehus K. et al. Cellular mechanisms in ischemic preconditioning: the role of adenosine and protein kinase C, in Das DK (ed): Cellular, Biochemical, and Molecular Aspects of Reperfusion Injury. New York Academy of Sciences 1994;82–98.Google Scholar
  2. 2.
    Gross GJ, Yao Z, Auchampach JA. Role of ATP-sensitive potassium channels in ischemic preconditioning, in Przyklenk K, Kloner (ed). Ischemic Preconditioning: the Concepts of Endogenous Cardioprotection, Develop Cardiovasc Med. Vol 148. Boston: Kluwer Academic Publishers, 1994:125–135.CrossRefGoogle Scholar
  3. 3.
    Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel?-Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res 1995;77:1030–1035.PubMedCrossRefGoogle Scholar
  4. 4.
    Liu Y, Gao WD, O’Rourke B et al. Synergistic modulation of ATP-sensitive K+ currents by protein kinase C and adenosine: implications for ischemic preconditioning. Circ Res 1996;78:443–454.PubMedCrossRefGoogle Scholar
  5. 5.
    Dunne MJ. Phorbol myristate acetate and ATP-sensitive potassium channels in insulin-secreting cells. Am J Physiol 1994;267:C501–C506.PubMedGoogle Scholar
  6. 6.
    Ribalet B, Eddlestone GT. Characterization of the G protein coupling of a somatostatin receptor to the K+ ATP channel in insulin-secreting mammalian HIT and RIN cell lines. J Physiol 1995;485:73–86.PubMedGoogle Scholar
  7. 7.
    Deutsch N, Weiss JN. ATP-sensitive K+ channel modification by metabolic inhibition in isolated guinea-pig ventricular myocytes. J Physiol 1993;465:163–179.PubMedGoogle Scholar
  8. 8.
    Wang YG, Lipsius SL. Acetylcholine activates a glibenclamide-sensitive K+ current in cat atrial myocytes. Am J Physiol 1995;268:H1322–H1334.PubMedGoogle Scholar
  9. 9.
    Hu K, Duan D, Nattel S. Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes. Circ Res 1996;78:492–498.PubMedCrossRefGoogle Scholar
  10. 10.
    Light PE, Sabir AA, Allen BG, et al. Protein kinase C-induced changes in the stoichiometry of ATP binding activated cardiac ATP-sensitive K channels: A possible mechanistic link to ischemic preconditioning. Circ Res 1996; 79:399–406.PubMedCrossRefGoogle Scholar
  11. 11.
    Findlay I. Sulphonylurea drugs no longer inhibit ATP-sensitive K channels during metabolic stress in cardiac muscle. J Pharmacol Exp Ther 1993;266:456–467.PubMedGoogle Scholar
  12. 12.
    Nichols CG, Ripoll C, Lederer WJ. ATP sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction. Circ Res 1991;68:280–287.PubMedCrossRefGoogle Scholar
  13. 13.
    Henry P, Puceat M, Demolombe S et al. Adenosine A1, stimulation activates ö-protein kinase C in rat ventricular myocytes. Circ Res 1996;78:161–165.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Yongge Liu
  • Wei Dong Gao
  • Brian O’Rourke
  • Eduardo Marban

There are no affiliations available

Personalised recommendations