Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Ferrari, R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Ferrari, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Healthy versus sick myocytes: metabolism, structure and function

R. Ferrari*

University of Ferrara, Ferrara, Italy

* Correspondence: Prof. Roberto Ferrari, Chair of Cardiology, University of Ferrara, Corso Giovecca, 203, 44100 Ferrara, Italy.

Abstract

The myocytes are extraordinary cells. They are immortal and contract for a lifetime, supporting the peripheral circulation. In order to do so, they have a unique ultrastructure and unique biochemical machinery that allows them to produce enough adenosine triphosphate to support the contraction. This article deals with the ultrastructure of cardiac muscle and myocytes, and with our current understanding of cardiac metabolism. In addition, the process of contraction is taken into consideration, as well as the mechanisms that allow the adult myocyte to be a terminal cell. However, even the myocytes can die; this can happen by necrosis as a result of an external insult (e.g. a lack of oxygen due to an abrupt occlusion of a coronary artery) or by apoptosis — a genetically programmed type of death that is operative in foetal life. Interestingly, and quite amazingly, under pathological conditions such as acute myocardial infarction or congestive heart failure, this genetic programme is reinstated and apoptosis can then occur, thus resembling features that occur un the embryonic phenotype. The metabolic alterations that occur under pathological conditions such as myocardial ischaemia are also addressed in depth, with several references to the so-called ‘new ischaemic syndromes’, such as stunning, hibernation and reperfusion paradox. The review is presented in light of an understanding of the biochemical and biomolecular changes that occur in pathological conditions, with the hope that this will provide room for innovative therapeutic intervention.

Key Words: Apoptosis • contraction • heart failure • hypertrophy • metabolism • myocyte • necrosis • remodelling

References

  1. Bossen E, Sommer JR, Waugh RA. Comparative stereology of the mouse and finch left ventricle. Tissue Cell. 1978;10:773–784[CrossRef][Web of Science][Medline]
  2. Bossen EH, Sommer JR, Waugh RA. Comparative stereology of mouse atria. Tissue Cell. 1981;13:71–77[CrossRef][Web of Science][Medline] [3]Somlyo AP, Somlyo AV, Gonzales-Serratos H, Shuman H, McLennan G. The sacroplasmic reticulum and its composition in resting and in contracting muscle. In: Muscle Contraction. Its Regulatory Mechanisms. Tokyo, Japan Scientific Societies Press; Berlin, Springer-Verlag: 421–433.
  3. Wendt-Gallitelli MF, Wolburg H. Electron probe microanalysis of frozen dried sections of heart muscle prepared using low temperature techniques. Scan Electron Microsc. 1981;II:455–462
  4. Mitchell P. Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation. Bodminster: Glynn Res. Ltd; 1966.
  5. Gunter TE, Pfeiffer DR. Mechanisms by which mitochondria transport calcium. Am J Physiol. 1990;258:C755–C786
  6. Hansford RG. Dehydrogenase activation by Ca++ in cells and tissues. J Bioenerg Biomembr. 1991;23:823–854[CrossRef][Web of Science][Medline]
  7. Bers DM. Excitation-Contraction Coupling and Cardiac Contractile Force. 2nd ed. Dordrecht: The Netherlands, Kluwer Academic; 2001.
  8. Fukuda N, Sasaki D, Ishiwata S, Kurihara S. Length dependence of tension generation in rat skinned cardiac muscle. Circ Res. 2001;104:1639–1645
  9. Bassani JWM, Bassani RA, Bers DM. Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanism. J Physiol. 1994;476:279–293[Abstract/Free Full Text]
  10. Brandes R, Bers DM. Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle. Circ Res. 1997;80:82–87[Abstract/Free Full Text]
  11. Hove-Madsen L, Bers DM. Sarcoplasmic reticulum Ca2+ uptake and thapsigargin sensitivity in permeabilized rabbit and rat ventricular myocytes. Circ Res. 1993;73:820–828[Abstract/Free Full Text]
  12. Li L, Chu G, Kranias EG, Bers DM. Cardiac myocyte calcium transport in phopholamban knockout mouse: relaxation and endogenous CaMKII effects. Am J Physiol. 1998;274:H1335–H1347
  13. Hasenfuss G. Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res. 1998;37:279–289[Free Full Text]
  14. Pogwizd SM, Schlotthauer K, Li L, Yuan W, Bers DM. Arrhythmogenesis and contractile dysfunction in heart failure: roles of sodium-calcium exchange, inward rectifier potassium current and residual ß-adrenergic responsiveness. Circ Res. 2001;88:1159–1167[Abstract/Free Full Text]
  15. Scriven DRL, Dan P, Moore EDW. Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J. 2000;79:2682–2691[Web of Science][Medline]
  16. Fruen BR, Bardy JM, Byrem TM, Strasburg GM, Louis CF. Differential Ca2+ sensitivity of skeletal and cardaac muscle ryanodine receptors in the presence of calmodulin. Am J Physiol. 2000;279:C724–C733[Web of Science]
  17. Marx SO, Reiken S, Hisamatsu Y, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in falling hearts. Cell. 2000;101:365–376[CrossRef][Web of Science][Medline]
  18. Marx SO, Reiken S, Hisamatsu Y, et al. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol. 2001;153:699–708[Abstract/Free Full Text]
  19. Meyers MB, Puri TS, Chein AJ, et al. Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ Channels. J Biol Chem. 1998;273:18930–18935[Abstract/Free Full Text]
  20. Zhang L, Kelly J, Schmeisser G, Kobayashi YM, Jones LR. Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane. J Biol Chem. 1997;272:23389–23397[Abstract/Free Full Text]
  21. Franzini-Armstrong C, Protasi F, Ramesh V. Shape, size, and distribution of Ca2+ release units and couplons in skeletal and cardiac muscles. Biophys J. 1999;77:1528–1539[Web of Science][Medline]
  22. Sipido KR, Carmeliet E, van de Werf F. T-type Ca2+ current as a trigger for Ca2+ release from the sarcoplasmic reticulum in guinea-pig ventricular myocytes. J Physiol. 1998;508:439–451[Abstract/Free Full Text]
  23. Zhou ZF, January CT. Both T- and L-type Ca2+ channels can contribute to excitation-contraction coupling in cardiac Purkinje cells. Biophys J. 1998;74:1830–1839[Web of Science][Medline]
  24. Li L, DeSantiago J, Chu G, Kranias EG, Bers DM. Phosphorylation of phospholamban and troponin I in ß-adrenergic-induced acceleration of cardiac relaxation. Am J Physiol. 2000;278:H769–H779[Web of Science]
  25. Soonpaa MH, Field LJ. Survey of studies examining mammalian cardiomyocyte DNA synthesis. Circ Res. 1998;83:15–26[Free Full Text]
  26. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–257[Web of Science][Medline]
  27. Searle J, Kerr JFR, Bishop CJ. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Annu. 1982;17:229–259
  28. Alles A, Alley K, Barrett JC, et al. Apoptosis: a general comment. FASEB J. 1991;5:2127–2128[Web of Science][Medline]
  29. Gerschenson LE, Rotello RJ. Apoptosis: a different type of cell death. FASEB J. 1992;6:2450–2455[Abstract]
  30. Eigenbrodt ML, Eigenbrodt EH, Thiele DL. Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. Am J Pathol. 1990;137:1065–1076[Abstract]
  31. Borgers M, Voipio-Pulkii LM, Izumo S. Spotlight on: apoptosis. Cardiovasc Res. 2000;45:525–804[Free Full Text]
  32. Majno G, Joris I. Apoptosis, oncosis and necrosis: an overview of cell death. Am J Pathol. 1995;146:3–15[Abstract]
  33. Haunstetter A, Izumo S. Apoptosis: basic mechanisms and implications for cardiovascular disease. Circulation. 1998;82:1111–1129
  34. Wolf BB, Green DR. Suicidal tendencies: apoptotic cell death by caspase family proteinases. J Biol Chem. 1999;274:20049–20052[Free Full Text]
  35. Nagata S. Fas ligand-induced apoptosis. Annu Rev Genet. 1999;33:29–55[CrossRef][Web of Science][Medline]
  36. Onoh M, Takemura G, Ohno H, et al. ‘Apoptotic’ myocytes in the infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation: analysis by immunogold electron microscopy combined with in situ end labeling. Circulation. 1998;98:1422–1430[Abstract/Free Full Text]
  37. Shaper J, Elsasser A, Kostin S. The role of cell death in heart failure. Circulation. 1999;85:867–869
  38. Aikawa R, Komuro I, Yamazaki T, et al. Oxidative stress activates extracellular signal-regulated kinases through src and ras in cultured cardiac myocytes of neonatal rats. J Clin Invest. 1997;100:1813–1821[Web of Science][Medline]
  39. Long X, Boluyt MO, Hipolito ML, et al. p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. J Clin Invest. 1997;99:2635–2643[Web of Science][Medline]
  40. Farber JL. Biology of disease: membrane injury and calcium homeostasis in the pathogenesis of coagulative necrosis. Lab Invest. 1982;47:114–123[Web of Science][Medline]
  41. Hillis LD, Braunwald E. Myocardial ischemia. N Engl J Med. 1977;296:971–978Hillis LD, Braunwald E. Myocardial ischemia. N Engl J Med. 1977;296:1034–1041Hillis LD, Braunwald E. Myocardial ischemia. N Engl J Med. 1977;296:1093–1096[Web of Science][Medline]
  42. Trump BF, Valigorsky JM, Dees JH, et al. Cellular change in human disease: a new method of pathological analysis. Hum Pathol. 1973;4:89–100[CrossRef][Web of Science][Medline]
  43. Sabbah HN. Apoptotic cell death in heart failure. Cardiovasc Res. 2000;45:704–712[Free Full Text]
  44. Olivetti G, Abbi R, Quaini F, et al. Apoptosis in the failing human heart. N Engl J Med. 1997;336:1131–1141[Abstract/Free Full Text]
  45. Guerra S, Leri A, Wang X, et al. Myocyte death in the failing human heart is gender dependent. Circ Res. 1999;85:856–866[Abstract/Free Full Text]
  46. Hearse DJ. Myocardial ischaemia: can we agree on a definition for the 21st century? Cardiovasc Res. 1994;28:1737–1744
  47. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation. 1989;80:1049–1062[Abstract/Free Full Text]
  48. Ferrari R, Hearse DJ. Reperfusion injury: does it exist and does it have clinical relevance? J Thromb Thrombolysis. 1997;4:25–34[CrossRef][Medline]
  49. Ferrari R, Cargnoni A, Bernocchi P, et al. Metabolic adaptation during a sequence of no-flow and low-flow ischaemia: a possible trigger for hibernation. Circulation. 1996;94:2587–2596[Abstract/Free Full Text]
  50. Braunwald E, Kloner RA. The stunned myocardium: prolonged, post-ischaemic ventricular dysfunction. Circulation. 1982;66:1146–1149[Abstract/Free Full Text]
  51. Bolli R. Mechanism of myocardial ‘stunning’. Circulation. 1990;82:723–738[Abstract/Free Full Text]
  52. Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion: evidence that m myocardial ‘stunning’ is a manifestation of reperfusion injury. Circ Res. 1989;65:607–622[Abstract/Free Full Text]
  53. Ferrari R, Pedersini P, Bongrazio M, et al. Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion. Basic Res Cardiol. 1993;88:495–512[CrossRef][Web of Science][Medline]
  54. Hearse DJ, Humphrey SM, Chain EB. Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: a study of myocardial enzyme release. J Mol Cell Cardiol. 1973;5:395–407[CrossRef][Web of Science][Medline]
  55. Siegmund B, Zude R, Piper HM. Recovery of anoxicreoxygenated cardiomyocytes from severe Ca2+ overload. Am J Physiol. 1992;63:H1262–H1269
  56. Piper HM, Balser C, Ladilov YV, et al. The role of exchange in ischaemia-reperfusion. Basic Res Cardiol. 1996;91:191–202[CrossRef][Web of Science][Medline]
  57. Ladilov YV, Siegmund B, Piper HM. Protection of the reoxygenated cardiomyocyte against hypercontracture by inhibition of exchange. Am J Physiol. 1995;268:H1531–H1539
  58. Ruiz-Meana M, Garcia-Dorado D, Gonzales MA, et al. Effect of osmotic stress on sarcolemmal integrity of isolated cardio-myocytes following transient metabolic inhibition. Cardiovasc Res. 1995;30:64–69[CrossRef][Web of Science][Medline]
  59. Rahimtoola SH. A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. Circulation. 1983;72:V123–V135
  60. van Binsbergen XA, van Emous JG, Ferari R, et al. Metabolic and functional consequences of successive no-flow and sustained low-flow ischaemia: a31 P MRS study on rat hearts. J Mol Cell Cardiol. 1996;28:2373–2381[CrossRef][Web of Science][Medline]
  61. Schulz R, Post H, Sakka S, et al. Intra-ischemic preconditioning: increased tolerance to sustained low-flow ischemia by a brief episode of no-flow ischemia without intermittent reperfusion. Circ Res. 1995;76:942–950[Abstract/Free Full Text]
  62. Koning MMG, Simonis LAJ, de Zeeuw S, et al. Ischaemic preconditioning by partial occlusion without intermittent reperfusion. Cardiovasc Res. 1991;28:1146–1151[CrossRef]
  63. Schulz R, Heusch G. Ischaemic preconditioning and myocardial hibernation: is there a common mechanism? Basic Res Cardiol. 1996;91:50–52[Web of Science][Medline]
  64. Heusch G, Ferrari R, Hearse DJ, et al. Myocardial hibernation: questions and controversies. Cardiovasc Res. 1997;36:301–309[Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Ferrari, R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Ferrari, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?