Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Study
  • Published:

KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 110–116 (2007)Cite this article

Abstract

Background A 53-year-old female presented with a 10-year history of paroxysmal atrial fibrillation (AF), precipitated by activity and refractory to medical therapy. In the absence of traditional risk factors for disease, a genetic defect in electrical homeostasis underlying stress-induced AF was explored.

Investigations Echocardiography, cardiac perfusion stress imaging, invasive electrophysiology with isoproterenol provocation, genomic DNA sequencing of KATP channel genes, exclusion of mutation in 2,000 individuals free of AF, reconstitution of channel defect with molecular phenotyping, and verification of pathogenic link in targeted knockout.

Diagnosis KATP channelopathy caused by missense mutation (Thr1547Ile) of the ABCC9 gene conferring predisposition to adrenergic AF originating from the vein of Marshall.

Management Disruption of arrhythmogenic gene–environment substrate at the vein of Marshall by radiofrequency ablation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mutation in ABCC9, which encodes the SUR2A KATP channel subunit, in a patient with AF originating from the vein of Marshall.
Figure 2: The ABCC9 mutation disrupts KATP channel function, with the disease phenotype verified in an adrenergically stressed gene knockout model.
Figure 3: Ablation of the vein of Marshall eliminated adrenergic AF in a patient with mutated KATP channels.

References

  1. Olson TM et al. (2006) Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum Mol Genet 15: 2185–2191

    Article  CAS  Google Scholar 

  2. Alekseev AE et al. (2005) ATP-sensitive K+ channel channel/enzyme multimer: metabolic gating in the heart. J Mol Cell Cardiol 38: 895–905

    Article  CAS  Google Scholar 

  3. Zingman LV et al. (2002) Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci USA 99: 13278–13283

    Article  CAS  Google Scholar 

  4. Bienengraeber M et al. (2004) ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet 36: 382–387

    Article  CAS  Google Scholar 

  5. Matsushita K et al. (2002) Intramolecular interaction of SUR2 subtypes for intracellular ADP-Induced differential control of KATP channels. Circ Res 90: 554–561

    Article  CAS  Google Scholar 

  6. Chugh SS et al. (2001) Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol 37: 371–378

    Article  CAS  Google Scholar 

  7. Roberts R (2006) Mechanisms of disease: genetic mechanisms of atrial fibrillation. Nat Clin Pract Cardiovasc Med 3: 276–282

    Article  CAS  Google Scholar 

  8. Chen YH et al. (2003) KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 299: 251–254

    Article  CAS  Google Scholar 

  9. Coumel P (1996) Autonomic influences in atrial tachyarrhythmias. J Cardiovasc Electrophysiol 7: 999–1007

    Article  CAS  Google Scholar 

  10. Doshi RN et al. (1999) Relation between ligament of Marshall and adrenergic atrial tachyarrhythmia. Circulation 100: 876–883

    Article  CAS  Google Scholar 

  11. Haissaguerre M et al. (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339: 659–666

    Article  CAS  Google Scholar 

  12. Inagaki N et al. (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16: 1011–1017

    Article  CAS  Google Scholar 

  13. Brundel BJ et al. (2001) Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J Am Coll Cardiol 37: 926–932

    Article  CAS  Google Scholar 

  14. Balana B et al. (2003) Decreased ATP-sensitive K+ current density during chronic human atrial fibrillation. J Mol Cell Cardiol 35: 1399–1405

    Article  CAS  Google Scholar 

  15. Liu XK et al. (2004) Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia. Diabetes 53 (Suppl 3): S165–S168

    Article  CAS  Google Scholar 

  16. Haissaguerre M et al. (2003) Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation 108: 925–928

    Article  Google Scholar 

  17. Ashcroft FM (2005) ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 115: 2047–2058

    Article  CAS  Google Scholar 

  18. Van Wagoner DR (1993) Mechanosensitive gating of atrial ATP-sensitive potassium channels. Circ Res 72: 973–983

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was approved by the Mayo Clinic Institutional Review Board and Institutional Animal Care and Use Committee. This work was supported by the National Institutes of Health, Marriott Heart Disease Research Program, Marriott Foundation and Mayo Clinic. AE Alekseev is affiliated with the Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Puschino, Russia, and C Moreau is currently at the French National Center for Scientific Research, Molecular and Cellular Biophysics, Grenoble, France.

Author information

Authors and Affiliations

  1. TM Olson is Associate Professor of Medicine and Pediatrics, AE Alekseev is Assistant Professor of Medicine and Pharmacology, C Moreau is Career Scientist, XK Liu is Clinician Investigator Scholar, LV Zingman is Assistant Professor of Medicine and Pharmacology, SJ Asirvatham and A Jahangir are Associate Professors of Medicine, and A Terzic is Marriott Family Professor of Cardiovascular Research and Professor of Medicine and Pharmacology, Mayo Clinic, Rochester, MN, USA.,

    Timothy M Olson, Alexey E Alekseev, Christophe Moreau, Xiaoke K Liu, Leonid V Zingman, Samuel J Asirvatham, Arshad Jahangir & Andre Terzic

  2. T Miki is Associate Professor, and S Seino is Professor of Cellular and Molecular Medicine, Kobe University, Kobe, Japan.,

    Takashi Miki & Susumu Seino

Authors
  1. Timothy M Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexey E Alekseev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christophe Moreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoke K Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leonid V Zingman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Miki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Susumu Seino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Samuel J Asirvatham
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arshad Jahangir
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andre Terzic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Timothy M Olson or Andre Terzic.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

Web links

Bienengraeber M et al. (2004) ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet 36: 382–387

Roberts R (2006) Mechanisms of disease: Genetic mechanisms of atrial fibrillation. Nat Clin Pract Cardiovasc Med 3: 276–282

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olson, T., Alekseev, A., Moreau, C. et al. KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation. Nat Rev Cardiol 4, 110–116 (2007). https://doi.org/10.1038/ncpcardio0792

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpcardio0792

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing