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Sealing the leak, healing the heart

Stabilization of the cardiac ryanodine receptor may represent a new concept in treating sudden cardiac death in several heart disorders.

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Figure 1: Exercise-induced diastolic calcium leak from the sarcoplasmic reticulum may induce delayed-after depolarizations (DADs) and fatal ventricular tachyarrhythmia in different cardiac disorders.

References

  1. Huikuri, H.V., Castellanos, A. & Myerburg, R.J. Sudden death due to cardiac arrhythmias. N. Engl. J. Med. 345, 1473–1482 (2001).

    Article  CAS  Google Scholar 

  2. Wehrens, X.H.T. et al. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113, 829–840 (2003).

    Article  CAS  Google Scholar 

  3. Valdivia, H.H., Kaplan, J.H., Ellis-Davies, G.C. & Lederer, W.J. Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation. Science 267, 1997–2000 (1995).

    Article  CAS  Google Scholar 

  4. Marks, A.R. Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death. J. Mol. Cell. Cardiol. 33, 615–624 (2001).

    Article  CAS  Google Scholar 

  5. Marx, S.O. et al. PKA phosphrylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101, 365–376 (2000).

    Article  CAS  Google Scholar 

  6. Reiken, S. et al. Beta-adrenergic receptor blockers restore cardiac calcium release channel (ryanodine receptor) structure and function in heart failure. Circulation 104, 2843–2848 (2001).

    Article  CAS  Google Scholar 

  7. Reiken, S. et al. Beta-blockers restore calcium release channel function and imporve cardiac muscle performance in human heart failure. Circulation 107, 2459–2466 (2003).

    Article  CAS  Google Scholar 

  8. Yano, M. et al. FKBP12.6-mediated stabilization of calcium-release channel (ryanodine receptor) as a novel therapeutic strategy against heart failure. Circulation 107, 477–484 (2003).

    Article  CAS  Google Scholar 

  9. Most, P. et al. Transgenic overexpression of the Ca2+ binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J. Biol. Chem.; published online 30 May 2003 (doi:10.1074/jbc.M301788200).

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Most, P., Koch, W. Sealing the leak, healing the heart. Nat Med 9, 993–994 (2003). https://doi.org/10.1038/nm0803-993

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