Skip to main content
SpringerLink
Log in

Potassium channel overexpression

  • Chapter
Molecular Approaches to Heart Failure Therapy

  • 93 Accesses

Abstract

Ion channels in the plasma membrane play a critical role in cellular function. These proteins are the gatekeepers that control ion homeostasis and shape excitability. Excitable cells use a variety of different ion channels to fashion their hallmark electrical signal, the action potential. Advances in molecular electrophysiology have led to the identification of more ion channel genes than there are identified membrane currents. This excess is particularly striking with potassium channels, where the wide diversity of genes is compounded by variable levels of hetero-multimerization, alternative splicing and post-translational modification. The classical methods of studying the roles of each gene rely either on exogenous expresison in frog oocytes or pharmacological manipulation of native currents. While these techniques have yielded a wealth of information concerning ion channel structure and function, they have come up short in linking individual genes and their products to physiology and disease.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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. Ahkong QF, et al (1987) Movements of fluorescent probes in the mechanism of cell fusion induced by poly(ethylene glycol). J Cell Sci 88 (Pt 3):389–398

    PubMed  CAS  Google Scholar 

  2. Antzelevitch C, et al (1991) Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ Res 69(6):1427–1449

    Article  PubMed  CAS  Google Scholar 

  3. Babila T, et al (1994) Assembly of mammalian voltage-gated potassium channels: evidence for an important role of the first transmembrane segment. Neuron 12(3):615–626

    Article  PubMed  CAS  Google Scholar 

  4. Barry DM, et al. (1995) Differential expression of voltage-gated K+-channel subunits in adult rat heart. Relation to functional K+ channels? Circ Res 77(2):361–369

    Article  PubMed  CAS  Google Scholar 

  5. Beukelman DJ, Näbauer M, Erdmann E (1993) Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure. Circ Res 73:386–394

    Article  Google Scholar 

  6. Chen ML, Hoshi T, Wu CF (1996) Heteromultimeric interactions among K+ channel subunits from Shaker and eag famillies in Xenopus oocytes. Neuron 17(3):535–542

    Article  PubMed  CAS  Google Scholar 

  7. Chung S, Saal DB, Kaczmarek KL (1995) Elimination of potassium channel expression by antisense oligonucleotides in a pituitary cell line. Proc Natl Acad Sci USA 92:5955–5959

    Article  PubMed  CAS  Google Scholar 

  8. Curran ME, et al (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80(5):795–803

    Article  PubMed  CAS  Google Scholar 

  9. Dixon JE, McKinnon D (1994) Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats. Circ Res 75(2):252–260

    Article  PubMed  CAS  Google Scholar 

  10. Dixon JE, et al (1996) Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current. Circ Res 79(4):659–668

    Article  PubMed  CAS  Google Scholar 

  11. Fiset C, Clark RB, Shimoni Y, Giles WR (1997) Shal-type channels contribute to the Ca-independent transient outward K current in rat ventricle. J Physiol 500(1):51–64

    PubMed  CAS  Google Scholar 

  12. Goshima K, et al (1984) Beating activity of heterokaryons between myocardial and non-myocardial cells in culture. Exp Cell Res 151(1):148–159

    Article  PubMed  CAS  Google Scholar 

  13. Herskowitz I (1987) Functional inactivation of genes by dominant negative mutations. Nature 329:219–222

    Article  PubMed  CAS  Google Scholar 

  14. Hoffman PL, Tabakoff B (1994) The role of the NMDA receptor in ethanol withdrawal. Exs 71:61–70

    PubMed  CAS  Google Scholar 

  15. Hoppe UC, et al (1999) Manipulation of cellular excitability by cell fusion: effects of rapid introduction of transient outward K+ current on the guinea pig action potential. Circ Res 84(8):964–972

    Article  PubMed  CAS  Google Scholar 

  16. Isacoff EY, Jan YN, Jan LY (1990) Evidence for the formation of heteromultimetric potassium channels in Xenopus oocytes. Nature 345:530–534

    Article  PubMed  CAS  Google Scholar 

  17. Johns DC, Nuss HB, Marban E (1997) Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs. J Biol Chem 272(50):31598–31603

    Article  PubMed  CAS  Google Scholar 

  18. Johns DC, et al (1999) Inducible genetic suppression of neuronal excitability. J Neurosci 19(5):1691–1697

    PubMed  CAS  Google Scholar 

  19. Johns DC, et al (1995) Adenovirus-mediated expression of a voltage-gated potassium channel in vitro (rat cardiac myocytes) and in vivo (rat liver). A novel strategy for modifying excitability. J Clin Invest 96(2):1152–1158

    Article  PubMed  CAS  Google Scholar 

  20. Kaab S, et al (1996) Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. Circ Res 78(2):262–273

    Article  PubMed  CAS  Google Scholar 

  21. Kass RS, Davies MP (1996) The role of ion channels in an inherited heart disease: molecular genetics of the long QT syndrome. Cardiovasc Res 32:443–454

    PubMed  CAS  Google Scholar 

  22. Lee TE, et al (1994) Structural determinant for assembly of mammalian K+ channels. Biophys J 66(Pt 1):667–673

    Article  PubMed  CAS  Google Scholar 

  23. Li M, Jan YN, Jan LY (1992) Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel. Science 257(5074): 1225–1230

    Article  PubMed  CAS  Google Scholar 

  24. Maletic-Savatic M, Lenn NJ, Trimmer JS (1995) Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. J Neurosci 15 (Pt 2):3840–3851

    PubMed  CAS  Google Scholar 

  25. Marban E (1999) Heart failure: the electrophysiologic connection. J Cardiovasc Electrophysiol 10(10):1425–1428

    Article  PubMed  CAS  Google Scholar 

  26. Mitcheson JS, Hancox JC, Levi AJ (1996) Action potentials, ion channel currents, and transverse tubule density in adult rabbit ventricular myocytes maintained for 6 days in cell culture. Pflugers Arch Eur J Physiol 431:814–827

    CAS  Google Scholar 

  27. Myerburg RJ, Castellanos A (1988) Cardiac arrest and sudden cardiac death. In: Braunwald E (ed) Heart Disease: The Textbook of Cardiovascular Medicine. Saunders, Philadelphia, pp 742–777

    Google Scholar 

  28. Nabauer M, et al (1996) Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle. Circulation 93(1):168–177

    Article  PubMed  CAS  Google Scholar 

  29. Negulescu D, et al (1998) Translation initiation of a cardiac voltage-gated potassium channel by internal ribosome entry. J Biol Chem 273(32):20109–20113

    Article  PubMed  CAS  Google Scholar 

  30. Nestler EJ, Berhow MT, Brodkin ES (1996) Molecular mechanisms of drug addiction - adaptations in signal transduction pathways. Molecular Psychiatry 1(3):190–199

    PubMed  CAS  Google Scholar 

  31. No D, Yao T-P, Evans RM (1996) Ecdysone-inducible gene expression in mammalian celsl and transgenic mice. Proc Natl Acad Sci USA 93:3346–3351

    Article  PubMed  CAS  Google Scholar 

  32. Nuss HB, Marban E, Johns DC (1999) Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes. J Clin Invest 103(6):889–896

    Article  PubMed  CAS  Google Scholar 

  33. Nuss HB, et al (1996) Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer: a prototype for gene therapy for disorders of cardiac excitability and contractility. Gene Therapy 3(10):900–912

    PubMed  CAS  Google Scholar 

  34. Panyi G, Deutsch C (1996) Assembly and suppression of endogenous Kv1.3 channels in human T cells. J Gen Physiol 107(3):409–420

    Article  PubMed  CAS  Google Scholar 

  35. Po S, et al (1993) Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current? Circ Res 72(6):1326–1336

    Article  PubMed  CAS  Google Scholar 

  36. Po S, et al (1992) Functional expression of an inactivating potassium channel cloned from human heart. Circ Res 71(3):732–736

    Article  PubMed  CAS  Google Scholar 

  37. Ribera AB (1996) Homogenous development of electrical excitability via heterogenous ion channel expression. J Neurosci 16(3):1123–1130

    PubMed  CAS  Google Scholar 

  38. Roden DM (1994) Risks and benefits of antiarrhythmic therapy. N Engl J Med 331:785–791

    Article  PubMed  CAS  Google Scholar 

  39. Sanguinetti MC, et al (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81(2):299–307

    Article  PubMed  CAS  Google Scholar 

  40. Serodio P, Vega-Saenz De Miera E, Rudy B (1996) Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain. J Neurophys 75(5):2174–2179

    CAS  Google Scholar 

  41. Sheng M, et al (1992) Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron 9(2):271–284

    Article  PubMed  CAS  Google Scholar 

  42. Spector PS, et al (1996) Fast inactivation causes rectification of the Ikr channel. J Gen Physiol 107:611–619

    Article  PubMed  CAS  Google Scholar 

  43. Tinker A, Jan YN, Jan LY (1996) Regions responsible for the assembly of inwardly rectifying potassium channels. Cell 87(5):857–868

    Article  PubMed  CAS  Google Scholar 

  44. Tomaselli GF, et al (1994) Sudden cardiac death in heart failure. The role of abnormal repolarization (76 refs). Circulation 90(5): 2534–2539

    Article  PubMed  CAS  Google Scholar 

  45. Tsaur ML, et al (1992) Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. Neuron 8(6): 1055–1067

    Article  PubMed  CAS  Google Scholar 

  46. Tu L, Santarelli V, Deutsch C (1995) Truncated K+ channel DNA sequences specifically suppress lymphocyte K+ channel gene expression. Biophys J 68(1):147–156

    Article  PubMed  CAS  Google Scholar 

  47. Tu L et al (1996) Voltage-gated K+ channels contain multiple intersubunit association sites. J Biol Chem 271(31):18904–18911

    Article  PubMed  CAS  Google Scholar 

  48. Uchida T (1988) Introduction of macromolecules into mammalian cells by cell fusion. Exp Cell Res 178(1):1–17

    Article  PubMed  CAS  Google Scholar 

  49. Wagner RW (1995) The state of the art in antisense research. Nature Medicine 1:1116–1118

    Article  PubMed  CAS  Google Scholar 

  50. Weidmann S (1970) Electrical constants of trabecular muscle from mammalian heart. J Physiol (Lond) 210(4):1041–1054

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Molecular and Cellular Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    U. C. Hoppe, H. B. Nuss, B. O’Rourke, E. Marbán & D. C. Johns

Authors
  1. U. C. Hoppe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. B. Nuss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. O’Rourke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Marbán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. C. Johns
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrum Innere Medizin, Abt. Kardiologie und Pneumologie, Georg-August-Universität Göttingen, Robert-Koch-Straße 40, Göttingen, D-37075, Germany

    Gerd Hasenfuss

  2. Section of Molecular and Cellular Cardiology, The Johns Hopkins University, 844 Ross Building, Baltimore, MD, 21205, USA

    Eduardo Marbán M.D., Ph.D. (Professor of Medicine and Physiology) (Professor of Medicine and Physiology)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hoppe, U.C., Nuss, H.B., O’Rourke, B., Marbán, E., Johns, D.C. (2000). Potassium channel overexpression. In: Hasenfuss, G., Marbán, E. (eds) Molecular Approaches to Heart Failure Therapy. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-57710-9_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-57710-9_14

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-63332-4

  • Online ISBN: 978-3-642-57710-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation