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. 1998 Dec 1;336(Pt 2):337–343. doi: 10.1042/bj3360337

Protein kinase C-dependent activation of KATP channel enhances adenosine-induced cardioprotection.

B T Liang 1
PMCID: PMC1219876  PMID: 9820809

Abstract

Prior activation of protein kinase C (PKC) can precondition the cardiac cell against injury during subsequent ischaemia. By using cultured chick ventricular cell model for simulated ischaemia and preconditioning, the present study investigated the biochemical mechanism underlying the PKC-mediated preconditioning. A 5 min exposure to PMA enhanced the ability of pinacidil to mediate cardioprotection during a subsequent 90 min period of ischaemia, which is consistent with a sustained activation of the KATP channel initiated by PKC. The brief prior exposure to PMA was also associated with an enhanced ability of the adenosine A1 or A3 receptor agonist 2-chloro-N6-cyclopentyladenosine or N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide to elicit a cardioprotective response during the subsequent ischaemia. In myocytes pretreated with PMA, the cardioprotection mediated by receptor agonist was blocked by the concomitant presence of KATP-channel antagonists glibenclamide or 5-hydroxydecanoic acid during the ischaemia. Thus the KATP channel acts downstream of the adenosine A1 and A3 receptors in mediating the protective effect due to prior PMA exposure. KATP channel activation is responsible for the adenosine receptor-mediated effect. PMA treatment had no effect on other A1 or A3 receptor-mediated effects such as the inhibition of adenylate cyclase, ruling out a direct stimulation of the receptor or G-protein by PMA. The present results indicate that prior stimulation of PKC causes a sustained KATP channel activation, which in turn renders the myocyte more responsive to the protective action of adenosine A1 and A3 receptor agonists during the subsequent ischaemia.

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Selected References

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  1. Armstrong S., Downey J. M., Ganote C. E. Preconditioning of isolated rabbit cardiomyocytes: induction by metabolic stress and blockade by the adenosine antagonist SPT and calphostin C, a protein kinase C inhibitor. Cardiovasc Res. 1994 Jan;28(1):72–77. doi: 10.1093/cvr/28.1.72. [DOI] [PubMed] [Google Scholar]
  2. Auchampach J. A., Grover G. J., Gross G. J. Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate. Cardiovasc Res. 1992 Nov;26(11):1054–1062. doi: 10.1093/cvr/26.11.1054. [DOI] [PubMed] [Google Scholar]
  3. Clerk A., Bogoyevitch M. A., Fuller S. J., Lazou A., Parker P. J., Sugden P. H. Expression of protein kinase C isoforms during cardiac ventricular development. Am J Physiol. 1995 Sep;269(3 Pt 2):H1087–H1097. doi: 10.1152/ajpheart.1995.269.3.H1087. [DOI] [PubMed] [Google Scholar]
  4. Cribier A., Korsatz L., Koning R., Rath P., Gamra H., Stix G., Merchant S., Chan C., Letac B. Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study. J Am Coll Cardiol. 1992 Sep;20(3):578–586. doi: 10.1016/0735-1097(92)90011-b. [DOI] [PubMed] [Google Scholar]
  5. Deutsch E., Berger M., Kussmaul W. G., Hirshfeld J. W., Jr, Herrmann H. C., Laskey W. K. Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features. Circulation. 1990 Dec;82(6):2044–2051. doi: 10.1161/01.cir.82.6.2044. [DOI] [PubMed] [Google Scholar]
  6. Ely S. W., Berne R. M. Protective effects of adenosine in myocardial ischemia. Circulation. 1992 Mar;85(3):893–904. doi: 10.1161/01.cir.85.3.893. [DOI] [PubMed] [Google Scholar]
  7. Gross G. J. ATP-sensitive potassium channels and myocardial preconditioning. Basic Res Cardiol. 1995 Mar-Apr;90(2):85–88. doi: 10.1007/BF00789438. [DOI] [PubMed] [Google Scholar]
  8. Grover G. J., Sleph P. G., Dzwonczyk S. Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors. Circulation. 1992 Oct;86(4):1310–1316. doi: 10.1161/01.cir.86.4.1310. [DOI] [PubMed] [Google Scholar]
  9. Hu K., Duan D., Li G. R., Nattel S. Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes. Circ Res. 1996 Mar;78(3):492–498. doi: 10.1161/01.res.78.3.492. [DOI] [PubMed] [Google Scholar]
  10. Jost L. M., Kirkwood J. M., Whiteside T. L. Improved short- and long-term XTT-based colorimetric cellular cytotoxicity assay for melanoma and other tumor cells. J Immunol Methods. 1992 Mar 4;147(2):153–165. doi: 10.1016/s0022-1759(12)80003-2. [DOI] [PubMed] [Google Scholar]
  11. Li G. C., Vasquez J. A., Gallagher K. P., Lucchesi B. R. Myocardial protection with preconditioning. Circulation. 1990 Aug;82(2):609–619. doi: 10.1161/01.cir.82.2.609. [DOI] [PubMed] [Google Scholar]
  12. Liang B. T. Protein kinase C-mediated preconditioning of cardiac myocytes: role of adenosine receptor and KATP channel. Am J Physiol. 1997 Aug;273(2 Pt 2):H847–H853. doi: 10.1152/ajpheart.1997.273.2.H847. [DOI] [PubMed] [Google Scholar]
  13. Liu Y., Gao W. D., O'Rourke B., Marban E. Synergistic modulation of ATP-sensitive K+ currents by protein kinase C and adenosine. Implications for ischemic preconditioning. Circ Res. 1996 Mar;78(3):443–454. doi: 10.1161/01.res.78.3.443. [DOI] [PubMed] [Google Scholar]
  14. Liu Y., Ytrehus K., Downey J. M. Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J Mol Cell Cardiol. 1994 May;26(5):661–668. doi: 10.1006/jmcc.1994.1078. [DOI] [PubMed] [Google Scholar]
  15. McCullough J. R., Normandin D. E., Conder M. L., Sleph P. G., Dzwonczyk S., Grover G. J. Specific block of the anti-ischemic actions of cromakalim by sodium 5-hydroxydecanoate. Circ Res. 1991 Oct;69(4):949–958. doi: 10.1161/01.res.69.4.949. [DOI] [PubMed] [Google Scholar]
  16. Miura T., Ogawa T., Iwamoto T., Shimamoto K., Iimura O. Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning. Circulation. 1992 Sep;86(3):979–985. doi: 10.1161/01.cir.86.3.979. [DOI] [PubMed] [Google Scholar]
  17. Murry C. E., Jennings R. B., Reimer K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124–1136. doi: 10.1161/01.cir.74.5.1124. [DOI] [PubMed] [Google Scholar]
  18. Ping P., Zhang J., Qiu Y., Tang X. L., Manchikalapudi S., Cao X., Bolli R. Ischemic preconditioning induces selective translocation of protein kinase C isoforms epsilon and eta in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity. Circ Res. 1997 Sep;81(3):404–414. doi: 10.1161/01.res.81.3.404. [DOI] [PubMed] [Google Scholar]
  19. Rybin V. O., Steinberg S. F. Protein kinase C isoform expression and regulation in the developing rat heart. Circ Res. 1994 Feb;74(2):299–309. doi: 10.1161/01.res.74.2.299. [DOI] [PubMed] [Google Scholar]
  20. Schulz R., Rose J., Heusch G. Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine. Am J Physiol. 1994 Oct;267(4 Pt 2):H1341–H1352. doi: 10.1152/ajpheart.1994.267.4.H1341. [DOI] [PubMed] [Google Scholar]
  21. Scudiero D. A., Shoemaker R. H., Paull K. D., Monks A., Tierney S., Nofziger T. H., Currens M. J., Seniff D., Boyd M. R. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res. 1988 Sep 1;48(17):4827–4833. [PubMed] [Google Scholar]
  22. Speechly-Dick M. E., Grover G. J., Yellon D. M. 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 Nov;77(5):1030–1035. doi: 10.1161/01.res.77.5.1030. [DOI] [PubMed] [Google Scholar]
  23. Stambaugh K., Jacobson K. A., Jiang J. L., Liang B. T. A novel cardioprotective function of adenosine A1 and A3 receptors during prolonged simulated ischemia. Am J Physiol. 1997 Jul;273(1 Pt 2):H501–H505. doi: 10.1152/ajpheart.1997.273.1.H501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Strickler J., Jacobson K. A., Liang B. T. Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors. J Clin Invest. 1996 Oct 15;98(8):1773–1779. doi: 10.1172/JCI118976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tomai F., Crea F., Gaspardone A., Versaci F., De Paulis R., Penta de Peppo A., Chiariello L., Gioffrè P. A. Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker. Circulation. 1994 Aug;90(2):700–705. doi: 10.1161/01.cir.90.2.700. [DOI] [PubMed] [Google Scholar]
  26. Yao Z., Gross G. J. A comparison of adenosine-induced cardioprotection and ischemic preconditioning in dogs. Efficacy, time course, and role of KATP channels. Circulation. 1994 Mar;89(3):1229–1236. doi: 10.1161/01.cir.89.3.1229. [DOI] [PubMed] [Google Scholar]

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