Skip to main content
SpringerLink
Log in

Genetic Engineering and Cardiac Ion Channels

  • Chapter
Cardiovascular Specific Gene Expression

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 214))

  • 68 Accesses

Abstract

In recent years there have been significant advances in our understanding of the molecular basis of the electrical activity of the heart with the cloning of many ion channel sub-units [1] and descriptions of their patterns of expression [2,31]. The situation now is such that our knowledge of individual ion channels considerably exceeds that of how they function in vivo and how their activities are co-ordinated to ensure normal cardiac activity. One important impetus to changing this state-of-affairs is the need for improved understanding of cardiac arrhythmias. Abnormalities of cardiac ion channel expression and function are known to contribute to the genesis of arrhythmias although it is not known precisely how [4].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barry DM, Nerbonne JM. Myocardial potassium channels: electrophysiological and molecular diversity. Annu Rev Physiol 1996; 58: 363–94.

    Article  PubMed  CAS  Google Scholar 

  2. Takimoto K, Li D, Hershman KM, Li P, Jackson EK, Levitan ES. Decreased expression of Kv4.2 and novel Kv4.3 K’ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Cire Res 1997; 81: 533–39.

    Article  CAS  Google Scholar 

  3. Gidh-Jain M, Huang B, Jain P, El-Sherif N. Differential expression of voltage-gated K’ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ Res 1996; 79: 669–75.

    Article  PubMed  CAS  Google Scholar 

  4. Grace AA, Chien KR. Congenital long QT syndromes. Toward molecular dissection of arrhythmia substrates. Circulation 1995; 92: 2786–89.

    Article  PubMed  CAS  Google Scholar 

  5. Tomaselli GF, Beuckelmann DJ, Calkins HG, Berger RD, Kessler PD, Lawrence JH, et al. Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 1994; 90: 2534–39.

    Article  PubMed  CAS  Google Scholar 

  6. Keating MT, Sanguinetti MC. Molecular genetic insights into cardiovascular disease. Science 1996; 272: 681–85.

    Article  PubMed  CAS  Google Scholar 

  7. Chien KR, Grace AA. Principles of cardiovascular molecular and cellular biology. In: Braunwald E, editor. Heart Disease. 5th ed. Philadelphia: W B Saunders, 1997: 1626–49.

    Google Scholar 

  8. Brugada J, Brugada P. Further characterization of the syndrome of right bundle branch block, ST segment elevation, and sudden cardiac death. J Cardiovasc Electrophys 1997;8:325-.31.

    Google Scholar 

  9. Chen Q, Kirsch GE, Zhang D, Brugada R et al. Genetic basis and molecular mechanism for idiopathic ventrcialr fibrillation. Nature 1998; 392: 293–96.

    Article  PubMed  CAS  Google Scholar 

  10. Colledge WH, Abella BS, Southern KW, Ratcliff R, Jiang C, Cheng SH, et al. Generation and characterization of a delta F508 cystic fibrosis mouse model. Nat Genet 1995; 10: 445–52.

    Article  PubMed  CAS  Google Scholar 

  11. Berul CI, Aronovitz MJ, Wang PJ, Mendelsohn ME. In vivo cardiac electrophysiological studies in the mouse. Circulation 1996; 94: 2641–48.

    Article  PubMed  CAS  Google Scholar 

  12. Restivo M. Animal models of the long QT syndrome. J Cardiovasc Electrophys 1997; 8: 115962.

    Google Scholar 

  13. James JF, Hewett TE, Robbins J. Cardiac physiology in transgenic mice. Circ Res 1998; 82: 407–15.

    Article  PubMed  CAS  Google Scholar 

  14. Saumarez RC, Vandenberg JI, Lowe MD, Taylor PJ, Ward DE, Camm AJ, et al. Electrogram fractionation in the long QT syndrome and as modelled in perfused heart by inhibition of inactivation of SCN5A-encoded ion channels. Submitted 1998.

    Google Scholar 

  15. Hart G. Cellular electrophysiology in cardiac hypertrophy and failure. Cardiovasc Res 1994; 28: 933–46.

    Article  PubMed  CAS  Google Scholar 

  16. Nabauer M, Beuckelmann DJ, Erdmann E. Characteristics of transient outward current in human ventricular myocytes from patients with terminal heart failure. Circ Res 1993; 73: 38694.

    Article  Google Scholar 

  17. Roden DM, George AL, Jr. The cardiac ion channels: relevance to management of arrhythmias. Annu Rev Med 1996; 47: 135–48.

    Article  PubMed  CAS  Google Scholar 

  18. Beuckelmann DJ, Nabauer M, Erdmann E. Alterations of K* currents in isolated human ventricular myocytes from patients with terminal heart failure. Circ Res 1993; 73: 379–85.

    Article  PubMed  CAS  Google Scholar 

  19. Schwartz PJ, Locati EH, Napolitano C, Priori SG. The long QT syndrome. In: Zipes DP, Jalife J, editors. Cardiac Electrophysiology: from cell to bedside. Philadelphia: WB Saunders Co., 1995: 788–811.

    Google Scholar 

  20. Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH. Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome. Circulation 1998; 97: 142–46.

    Article  PubMed  CAS  Google Scholar 

  21. Wang Q, Shen J, Spiawski I, Atkinson D, Li Z, Robinson JL, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995; 80: 805–11.

    Article  PubMed  CAS  Google Scholar 

  22. Bennett PB, Yazawa K, Makita N, George AL, Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature 1995; 376: 683–85.

    Article  PubMed  CAS  Google Scholar 

  23. Miller C. The inconstancy of the human heart. Nature 1996; 379: 767–68.

    Article  PubMed  Google Scholar 

  24. El Sherif N, Caref EB, Yin H, Restivo M. The electrophysiological mechanism of ventricular arrhythmias in the long QT syndrome. Tridimensional mapping of activation and recovery patterns. Circ Res 1996; 79: 474–92.

    Article  PubMed  Google Scholar 

  25. Saumarez RC, Heald S, Gill J, Slade AK, de Beider M, Walczak F, et al. Primary ventricular fibrillation is associated with increased paced right ventricular electrogram fractionation. Circulation 1995; 92: 2565–71.

    Article  PubMed  CAS  Google Scholar 

  26. Domanski MJ, Zipes DP, Schron E. Treatment of sudden cardiac death. Current understandings from randomized trials and future research directions. Circulation 1997; 95: 2694–99.

    Article  PubMed  CAS  Google Scholar 

  27. Saumarez RC, Slade AK, Grace AA, Sadoul N, Camm AJ, McKenna WJ. The significance of paced electrogram fractionation in hypertrophie cardiomyopathy. A prospective study. Circulation 1995; 91: 2762–68.

    Article  PubMed  CAS  Google Scholar 

  28. Saumarez RC, Slade AKB, McKenna WJ. Arrhythmias in hypertrophie cardiomyopathy. In: Podrid P, Kowey P, editors. Cardiac Arrhythmia: mechanisms, diagnosis and management. Baltimore: Williams and Wilkins, 1995: 1095–1109.

    Google Scholar 

  29. Bhandari AK, Shapiro WA, Morady F, Shen EN, Mason J, Scheinman MM. Electrophysiologic testing in patients with the long QT syndrome. Circulation 1985; 71: 63–71.

    Article  PubMed  CAS  Google Scholar 

  30. Gardner PI, Ursell PC, Fenoglio JJ, Jr., Wit AL. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. Circulation 1985; 72: 596611.

    Google Scholar 

  31. Bethell HWL, Vandenberg JI, Smith GA, Grace AA. Changes in ventricular repolarization during acidosis and low-flow ischemia. Am J Physiol 1998; 275: H551–61.

    PubMed  CAS  Google Scholar 

  32. Priori SG, Napolitano C, Cantu F, Brown AM, Schwartz PJ. Differential response to Na+ channel blockade, beta-adrenergic stimulation, and rapid pacing in a cellular model mimicking the SCN5A and BERG defects present in the long-QT syndrome. Circ Res 1996; 78: 1009–15.

    Article  PubMed  CAS  Google Scholar 

  33. Hanck DA, Sheets MF. Modification of inactivation in cardiac sodium channels: ionic current studies with Anthopleurin-A toxin. J Gen Physiol 1995; 106: 601–16.

    Article  PubMed  CAS  Google Scholar 

  34. Nuss HB, Marban E. Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture. J Phys Lond 1994; 479: 265–79.

    Google Scholar 

  35. Wang L, Feng Z, Kondo CS, Sheldon RS, Duff HJ. Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res 1996; 79: 79–85.

    Article  PubMed  CAS  Google Scholar 

  36. Wang L, Duff HJ. Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes. Am-J-Physiol 1996; 270: H2088–93.

    PubMed  CAS  Google Scholar 

  37. London B, Jeron A, Zhou J, Buckett P, Han X, Mitchell GF, et al. Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel. Proc Natl Acad Sci USA 1998; 95: 2926–31.

    Article  CAS  Google Scholar 

  38. Vetter DE, Mann JR, Wangemann P, Liu J, McLaughlin KJ, Lesage F, et al. Inner ear defects induced by null mutaion of the isK gene. Neuron 1996; 17: 1251–64.

    Article  PubMed  CAS  Google Scholar 

  39. Guerrero PA, Schuessler RB, Davis LM, Beyer EC, Johnson CM, Yamada KA, et al. Slow ventricular conduction in mice heterozygous for a connexin43 null mutation. J Clin Invest 1997; 99: 1991–98.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Andrew A. Grace
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard C. Saumarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jamie I. Vandenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Pieter A. Doevendans

  2. Academic Hospital Maastricht, CARIM, Maastricht, The Netherlands

    Robert S. Reneman

  3. Department of Physiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Marc van Bilsen

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Grace, A.A., Saumarez, R.C., Vandenberg, J.I. (1999). Genetic Engineering and Cardiac Ion Channels. In: Doevendans, P.A., Reneman, R.S., van Bilsen, M. (eds) Cardiovascular Specific Gene Expression. Developments in Cardiovascular Medicine, vol 214. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9321-2_16

Download citation

  • DOI: https://doi.org/10.1007/978-94-015-9321-2_16

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5189-9

  • Online ISBN: 978-94-015-9321-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation