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The possible role of phospholipase A2 in cardiac membrane destabilization under calcium overload conditions

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Summary

The mechanism of spontaneous diastolic depolarizations induced by different Ca2+ overloading conditions (ouabain toxicity, calcium ionophore A23187, O-K, high Ca2+ solution) in mammalian working myocardium fibres was studied with conventional microelectrode technique and pharmacological approach.

Antagonistic properties of antiphospholipase-A2 (PL A2)-active compounds (dexamethasone and indomethacin) were tested. Membrane oscillation in Ca2+ overload conditions were shown to be eliminated or largely protected by both anti-inflammatory agents. There was no influence of the compounds on electrical parameters and ion currents in intact mammalian and amphibian myocardium. The data obtained suggested that modulation of Ca2+-dependent PL A2 activity may contribute significantly to membrane destabilization due to Ca2+ overload of cardiac cells. An analogous membrane destabilizing action of exogenous PL A2 observed in Langendorff-perfused guinea pig heart is in favour of the hypothesis introduced.

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References

  1. Beckman JK, Owens K, Knauer TE, Weglicki WW (1982) Hydrolysis of sarcolemma by lysosomal lipases and inhibition by chlorpromazine. Am J Physiol 242:H652-H656

    PubMed  Google Scholar 

  2. Bhattacharyya ML, Vassalle M (1981) The effect of local anesthetics on strophanthidin toxicity in canine cardiac Purkinje fibres. J Physiol 312:125–142

    PubMed  Google Scholar 

  3. Blackwell GJ et al (1982) Glucocorticoids induce the formation and release of anti-inflammatory and anti-phospholipase proteins into the peritoneal cavity of the rat. Br J Pharmac 76:185–194

    Google Scholar 

  4. Bolli R (1982) Protection of ischemic myocardium in experimental animals and in man: a review. Cardiovasc Res Center Bul 21:1–33

    Google Scholar 

  5. Brown BS (1982) Early afterdepolarization induced by batrachotoxin: possible involvement of a sodium current. Fed Proc 42:581

    Google Scholar 

  6. Chien KR, Reeves JP, Buja M, Bonle F, Parkey R, Willerson JT (1981) Phospholipid alteration in canine ischemic myocardium. Circ Res 48: 711–719

    PubMed  Google Scholar 

  7. Cheung WY (1980) Calmodulin plays a pivotal role in cellular regulation. Science 207:19–27

    PubMed  Google Scholar 

  8. Brum G, Flockerzi, Hoffman F, Osterrieder W, Trautwein W (1983) Injection of catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes. Pflügers Arch 398:147–154

    Article  Google Scholar 

  9. Clusin WT, Bristow MR, Karagueuzian HS, Katzung BG, Schroeder JS (1982) Do calcium-dependent ionic currents mediate ischemic ventricular fibrillation? Am J Cardiol 49:606–611

    Article  PubMed  Google Scholar 

  10. Cranefield PF (1977) Action potentials, afterpotentials and arrhythmias. Circ Res 41:415–423

    PubMed  Google Scholar 

  11. Eisner DA, Lederer WJ (1979) Inotropic and arrhythmogenic effect of potassium-depleted solutions on mammalian cardiac muscle. J Physiol 294:255–277

    PubMed  Google Scholar 

  12. Ferrier GR (1977) Digitalis arrhythmias: Role of oscillatory afterpotentials. Progress in cardiovascular diseases. 19:459–479

    Article  PubMed  Google Scholar 

  13. Filippov AK, Porotikov VI (1983) Hormonal regulation of calcium channels in cardiac membranes. Biofisika28:675–678

    Google Scholar 

  14. Filippov AK, Porotikov VI (1983) Voltage clamp analysis of repetitive firing in frog atrial trabeculae. Gen Physiol Biophys 12:95–106

    Google Scholar 

  15. Flower R (1978) Steroidal antiinflammatory drugs as inhibitors of phospholipase A2. Advances in Prostaglandin and Thromboxane Res, 3 (ed by Galli C et al.) Raven Press, New York, 105–112

    Google Scholar 

  16. Franson RC, Pang DC, Weglicki WB (1979) Modulation of lipolytic activity in isolated canine cardiac sarcolemma by isoproterenol and propranolol. Bioch Bioph Res Comm 90:956–962

    Article  Google Scholar 

  17. Franson RC (1980) Inhibition of highly purified mammalian phospholipase A2 by non-steroidal anti-inflammatory agents. Bioch J 186:633–636

    Google Scholar 

  18. Heistracher P, Pillat B (1962) Elektrophysiologische Untersuchungen über die Wirkung von Chinidin auf die Aconitinvergiftung von Herzmuskelfasern. Naunyn-Schmiedeberg's Arch exp Path Pharm 244:48–62

    Article  Google Scholar 

  19. Irvine RF (1982) How is the level of free arachidonic acid controlled in mammalian cells? Biochem J 204:3–16

    PubMed  Google Scholar 

  20. Ito K, Kapaki H, Urakawa N (1979) Effects of palytoxin on mechanical and electrical activities of guinea pig papillary muscle. Jap J Pharmacol 29:467–476

    PubMed  Google Scholar 

  21. Lederer WJ, Tsien RW (1976) Transient inward current underlying arrhythmogenic effect of cardiotonic steroids in Purkinje fibres. J Physiol 263:73–100

    PubMed  Google Scholar 

  22. Kass KS, Tsien RW (1982) Fluctuations in membrane current driven by intracellular calcium in cardiac Purkinje fibers: Bioph J 381:259–269

    Google Scholar 

  23. Katz AM, Messineo FC (1981) Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48:1–16

    PubMed  Google Scholar 

  24. Kanazir DT, Stepic NR (1982) Extragenomic effect of glucocorticoids. Prog Clin Biol. Res 102:193–205

    Google Scholar 

  25. Kaplan L, Weiss J, Elsbash P (1978) Low concentrations of indomethacin inhibit phospholipase A2 of rabbit polymorphonuclear leukocytes. Proc Natl Acad Sci USA 75:2955–2958

    PubMed  Google Scholar 

  26. Karagueuzian HS, Katzung BG (1981) Relative inotropic and arrhythmogenic effect of five cardiac steroids in ventricular myocardium: oscillatory afterpotentials and the role of endogenous catecholamines. J Pharmacol Exp Ther 218:348–356

    PubMed  Google Scholar 

  27. Kretsinger RH (1981) Mechanisms of selective signalling by calcium. Neurosciences Research Program 217–327

  28. Rosen MR, Danilo P, Alonso M, Pippenger CE (1976) Effect of therapeutic concentrations of diphenylhydantion on transmembrane potentials of normal and depressed Purkinje fibers. J Pharmac Exp Ther 197:594–604

    Google Scholar 

  29. Rosen M, Danilo P (1980) Effects of tetrodotoxin, lidocain, verapamil, and AHR-2666 on ouabain-induced delayed afterdepolarization in canine Purkinje fibers. Circ Res 46:117–124

    PubMed  Google Scholar 

  30. Ruff RL, Stühmer W, Almers W (1982) Effect of glucocorticoid treatment on the excitability of rat skeletal muscle. Pflügers Arch 395:132–137

    Article  Google Scholar 

  31. Rougier O, Vassort G, Stampfli R (1968) Voltage clamp experiments of frog atrial heart muscle fibres with the sucrose gap technique. Pflügers Arch 301:91–108

    Article  Google Scholar 

  32. Saxon ME, Vorobiev SI, Beloyartsev FF, Baum OV (1981) The role of phospholipase A2 in cardiac arrhythmias. 8th International Congress of Electrocardiology. Budapest, Hungary, Abstracts p 41

  33. Saxon ME, Vorobiev SI (1984) Triggered arrhythmias induced with exogenous phospholipase A2 in Langendorff perfused hearts and their pharmacological analysis. Basic Res Cardiol, in press

  34. Saxon ME (1983) Efficiency of antiphospholipase A2 active compounds in stabilization of cardiac membrane under digitalis toxicity. 10th International Congress on Electrocardiology, Bratislava, Czechoslovakia, p 210

  35. Schaffer SW, Burton KP, Jones HP, Oel HH (1983) Phenothiazine protection in calcium overload-induced heart failure: a possible role for calmodulin. Am J Physiol 244:H328-H334

    PubMed  Google Scholar 

  36. Shier T (1982) Cytolytic mechanisms: self-destruction of mammalian cells by activation of endogenous hydrolytic enzymes. J Toxicol-Toxin, Reviews 1:1–32

    Google Scholar 

  37. Vanderhock JY, Feinstein MB (1979) Local anesthetics, chlorpromazine and propranolol inhibit stimulus activation of phospholipase A2 in human platelets. Mol Pharmacol 16:171–180

    PubMed  Google Scholar 

  38. Wasserstrom JA, Ferrier GR (1982) Effects of phenytoin and quinidine on digitalis-induced oscillatory afterpotentials, aftercontractions and inotropy in canine ventricular tissues. J Mol Cell Cardiol 14:725–736

    Article  PubMed  Google Scholar 

  39. Wightman PD, Dahlgren ME, Bonney RJ (1982) Protein kinase activation of phospholipase A2 in sonicates of mouse peritoneal macrophages. J Biol Chem 257:6650–6652

    PubMed  Google Scholar 

  40. Wong PY-K, Cheung WY (1979) Calmodulin stimulates human platelet phospholipase A2. Bioch Biophys Res Com 90:473–480

    Article  Google Scholar 

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Saxon, M.E., Filippov, A.K. & Porotikov, U.I. The possible role of phospholipase A2 in cardiac membrane destabilization under calcium overload conditions. Basic Res Cardiol 79, 668–678 (1984). https://doi.org/10.1007/BF01908384

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