Skip to main content
SpringerLink
Log in
Book cover

Bioinformatics and Drug Discovery pp 309–335Cite as

Models of Excitation–Contraction Coupling in Cardiac Ventricular Myocytes

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 910))

Abstract

Excitation–contraction coupling describes the processes relating to electrical excitation through force generation and contraction in the heart. It occurs at multiple levels from the whole heart, to single myocytes and down to the sarcomere. A central process that links electrical excitation to contraction is calcium mobilization. Computational models that are well grounded in experimental data have been an effective tool to understand the complex dynamics of the processes involved in excitation–contraction coupling.

Presented here is a summary of some computational models that have added to the understanding of the cellular and subcellular mechanisms that control ventricular myocyte calcium dynamics. Models of cardiac ventricular myocytes that have given insight into termination of calcium release and interval–force relations are discussed in this manuscript. Computational modeling of calcium sparks, the elementary events in cardiac excitation–contraction coupling, has given insight into mechanism governing their dynamics and termination as well as their role in excitation–contraction coupling and is described herein.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544

    PubMed  CAS  Google Scholar 

  2. Williams GS, Smith GD, Sobie EA, Jafri MS (2010) Models of cardiac excitation–contraction coupling in ventricular myocytes. Math Biosci 226:1–15

    Article  PubMed  CAS  Google Scholar 

  3. DiFrancesco D, Noble D (1985) A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci 307:353–398

    Article  PubMed  CAS  Google Scholar 

  4. Beeler GW, Reuter H (1977) Reconstruction of the action potential of ventricular myocardial fibres. J Physiol 268:177–210

    PubMed  CAS  Google Scholar 

  5. Luo CH, Rudy Y (1991) A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circ Res 68:1501–1526

    Article  PubMed  CAS  Google Scholar 

  6. Luo CH, Rudy Y (1994) A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res 74:1071–1096

    Article  PubMed  CAS  Google Scholar 

  7. Livshitz LM, Rudy Y (2007) Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents. Am J Physiol Heart Circ Physiol 292:H2854–H2866

    Article  PubMed  CAS  Google Scholar 

  8. Faber GM, Silva J, Livshitz L, Rudy Y (2007) Kinetic properties of the cardiac L-type Ca2+ channel and its role in myocyte electrophysiology: a theoretical investigation. Biophys J 92:1522–1543

    Article  PubMed  CAS  Google Scholar 

  9. Decker KF, Heijman J, Silva JR, Hund TJ, Rudy Y (2009) Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium. Am J Physiol Heart Circ Physiol 296:H1017–H1026

    Article  PubMed  CAS  Google Scholar 

  10. Zeng J, Rudy Y (1995) Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophys J 68:949–964

    Article  PubMed  CAS  Google Scholar 

  11. Barcenas-Ruiz L, Wier WG (1987) Voltage dependence of intracellular [Ca2+]i transients in guinea pig ventricular myocytes. Circ Res 61:148–154

    Article  PubMed  CAS  Google Scholar 

  12. Fabiato A (1985) Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol 85:247–289

    Article  PubMed  CAS  Google Scholar 

  13. Stern MD (1992) Theory of excitation–contraction coupling in cardiac muscle. Biophys J 63:497–517

    Article  PubMed  CAS  Google Scholar 

  14. Rice JJ, Jafri MS, Winslow RL (1999) Modeling gain and gradedness of Ca2+ release in the functional unit of the cardiac diadic space. Biophys J 77:1871–1884

    Article  PubMed  CAS  Google Scholar 

  15. Jafri MS, Rice JJ, Winslow RL (1998) Cardiac Ca2+ dynamics: the roles of ryanodine receptor adaptation and sarcoplasmic reticulum load. Biophys J 74:1149–1168

    Article  PubMed  CAS  Google Scholar 

  16. Imredy JP, Yue DT (1994) Mechanism of Ca(2+)-sensitive inactivation of L-type Ca2+ channels. Neuron 12:1301–1318

    Article  PubMed  CAS  Google Scholar 

  17. Gyorke I, Gyorke S (1998) Regulation of the cardiac ryanodine receptor channel by luminal Ca2+ involves luminal Ca2+ sensing sites. Biophys J 75:2801–2810

    Article  PubMed  CAS  Google Scholar 

  18. Gyorke S, Fill M (1993) Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart. Science 260:807–809

    Article  PubMed  CAS  Google Scholar 

  19. Franzini-Armstrong C, Protasi F, Ramesh V (1999) Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J 77:1528–1539

    Article  PubMed  CAS  Google Scholar 

  20. Marx SO, Gaburjakova J, Gaburjakova M, Henrikson C, Ondrias K, Marks AR (2001) Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res 88:1151–1158

    Article  PubMed  CAS  Google Scholar 

  21. Keizer J, Levine L (1996) Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys J 71:3477–3487

    Article  PubMed  CAS  Google Scholar 

  22. Keizer J, Smith GD (1998) Spark-to-wave transition: saltatory transmission of calcium waves in cardiac myocytes. Biophys Chem 72:87–100

    Article  PubMed  CAS  Google Scholar 

  23. Rice JJ, Jafri MS, Winslow RL (2000) Modeling short-term interval-force relations in cardiac muscle. Am J Physiol Heart Circ Physiol 278:H913–H931

    PubMed  CAS  Google Scholar 

  24. Groff JR, Smith GD (2008) Ryanodine receptor allosteric coupling and the dynamics of calcium sparks. Biophys J 95:135–154

    Article  PubMed  CAS  Google Scholar 

  25. Tran K, Smith NP, Loiselle DS, Crampin EJ (2009) A thermodynamic model of the cardiac sarcoplasmic/endoplasmic Ca(2+) (SERCA) pump. Biophys J 96:2029–2042

    Article  PubMed  CAS  Google Scholar 

  26. Smith GD, Keizer JE, Stern MD, Lederer WJ, Cheng H (1998) A simple numerical model of calcium spark formation and detection in cardiac myocytes. Biophys J 75:15–32

    Article  PubMed  CAS  Google Scholar 

  27. Wagner J, Keizer J (1994) Effects of rapid buffers on Ca2+ diffusion and Ca2+ oscillations. Biophys J 67:447–456

    Article  PubMed  CAS  Google Scholar 

  28. Buckley NM, Penefsky ZJ, Litwak RS (1972) Comparative force–frequency relationships in human and other mammalian ventricular myocardium. Pflugers Arch 332:259–270

    Article  PubMed  CAS  Google Scholar 

  29. Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 75:434–442

    Article  PubMed  CAS  Google Scholar 

  30. Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation–contraction coupling in heart muscle. Science 262:740–744

    Article  PubMed  CAS  Google Scholar 

  31. Stern MD, Song LS, Cheng H, Sham JS, Yang HT, Boheler KR, Rios E (1999) Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors. J Gen Physiol 113:469–489

    Article  PubMed  CAS  Google Scholar 

  32. Valdivia HH, Kaplan JH, Ellis-Davies GC, Lederer WJ (1995) Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation. Science 267:1997–2000

    Article  PubMed  CAS  Google Scholar 

  33. Sobie EA, Dilly KW, dos Santos Cruz J, Lederer WJ, Jafri MS (2002) Termination of cardiac Ca(2+) sparks: an investigative mathematical model of calcium-induced calcium release. Biophys J 83:59–78

    Article  PubMed  CAS  Google Scholar 

  34. Niggli E, Lederer WJ (1990) Voltage-independent calcium release in heart muscle. Science 250:565–568

    Article  PubMed  CAS  Google Scholar 

  35. Winslow RL, Scollan DF, Holmes A, Yung CK, Zhang J, Jafri MS (2000) Electrophysiological modeling of cardiac ventricular function: from cell to organ. Annu Rev Biomed Eng 2:119–155

    Article  PubMed  CAS  Google Scholar 

  36. Trayanova NA (2011) Whole-heart modeling: applications to cardiac electrophysiology and electromechanics. Circ Res 108:113–128

    Article  PubMed  CAS  Google Scholar 

  37. Silva JR, Rudy Y (2010) Multi-scale electrophysiology modeling: from atom to organ. J Gen Physiol 135:575–581

    Article  PubMed  CAS  Google Scholar 

  38. Hunter PJ, Pullan AJ, Smaill BH (2003) Modeling total heart function. Annu Rev Biomed Eng 5:147–177

    Article  PubMed  CAS  Google Scholar 

  39. McCulloch AD, Paternostro G (2005) Cardiac systems biology. Ann N Y Acad Sci 1047:283–295

    Article  PubMed  CAS  Google Scholar 

  40. Luo CH, Rudy Y (1994) A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation. Circ Res 74:1097–1113

    Article  PubMed  CAS  Google Scholar 

  41. Priori SG (2010) The fifteen years of discoveries that shaped molecular electrophysiology: time for appraisal. Circ Res 107:451–456

    Article  PubMed  CAS  Google Scholar 

  42. Roberts JD, Gollob MH (2010) The genetic and clinical features of cardiac channelopathies. Future Cardiol 6:491–506

    Article  PubMed  Google Scholar 

  43. Clancy CE, Rudy Y (2002) Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 105:1208–1213

    Article  PubMed  Google Scholar 

  44. Nuyens D, Stengl M, Dugarmaa S, Rossenbacker T, Compernolle V, Rudy Y, Smits JF, Flameng W, Clancy CE, Moons L, Vos MA, Dewerchin M, Benndorf K, Collen D, Carmeliet E, Carmeliet P (2001) Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat Med 7:1021–1027

    Article  PubMed  CAS  Google Scholar 

  45. Clancy CE, Rudy Y (2001) Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death. Cardiovasc Res 50:301–313

    Article  PubMed  CAS  Google Scholar 

  46. Clancy CE, Rudy Y (1999) Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia. Nature 400:566–569

    Article  PubMed  CAS  Google Scholar 

  47. Clancy CE, Zhu ZI, Rudy Y (2007) Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation. Am J Physiol Heart Circ Physiol 292:H66–H75

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Systems Biology, George Mason University, Manassas, VA, USA

    M. Saleet Jafri

Authors
  1. M. Saleet Jafri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Saleet Jafri .

Editor information

Editors and Affiliations

  1. , Department of Pathology, The University of New Mexico, Camino de Salud 915, Albuquerque, 87131, New Mexico, USA

    Richard S. Larson

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this protocol

Cite this protocol

Jafri, M.S. (2012). Models of Excitation–Contraction Coupling in Cardiac Ventricular Myocytes. In: Larson, R. (eds) Bioinformatics and Drug Discovery. Methods in Molecular Biology, vol 910. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-965-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-965-5_14

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-964-8

  • Online ISBN: 978-1-61779-965-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation