The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Ryanodine Receptor Phosphorylation by Calcium/Calmodulin-Dependent Protein Kinase II Promotes Life-Threatening Ventricular Arrhythmias in Mice With Heart Failure
Open accessAbstract
Background: Approximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca 2+ release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca 2+ remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca 2+ /calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias. Methods and Results: Mice in which the S2814 Ca 2+ /calmodulin-dependent protein kinase II site on RyR2 is constitutively activated (S2814D) develop pathological sarcoplasmic reticulum Ca 2+ release events, resulting in reduced sarcoplasmic reticulum Ca 2+ load on confocal microscopy. These Ca 2+ release events are associated with increased RyR2 open probability in lipid bilayer preparations. At baseline, young S2814D mice have structurally and functionally normal hearts without arrhythmias; however, they develop sustained ventricular tachycardia and sudden cardiac death on catecholaminergic provocation by caffeine/epinephrine or programmed electric stimulation. Young S2814D mice have a significant predisposition to sudden arrhythmogenic death after transverse aortic constriction surgery. Finally, genetic ablation of the Ca 2+ /calmodulin-dependent protein kinase II site on RyR2 (S2814A) protects mutant mice from pacing-induced arrhythmias versus wild-type mice after transverse aortic constriction surgery. Conclusions: Our results suggest that Ca 2+ /calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca 2+ release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure.
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Cites
Cardiac excitation–contraction coupling
Bers, D. M. (2002) · Nature · doi:10.1038/415198a · Cited by 4,744
Self-citationPKA Phosphorylation Dissociates FKBP12.6 from the Calcium Release Channel (Ryanodine Receptor)
Marx, S. O., Reiken, S., Hisamatsu, Y., Jayaraman, T., Burkhoff, D., Rosemblit, N., & Marks, A. R. (2000) · Cell · doi:10.1016/s0092-8674(00)80847-8 · Cited by 1,978
Wehrens, X. H. T., Lehnart, S. E., Huang, F., Vest, J. A., Reiken, S. R., Mohler, P. J., Sun, J., Guatimosim, S., Song, L.-S., Rosemblit, N., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00434-3 · Cited by 764
Self-citationAi, X., Curran, J. W., Shannon, T. R., Bers, D. M., & Pogwizd, S. M. (2005) · Circulation Research · doi:10.1161/01.res.0000194329.41863.89 · Cited by 697
Self-citationWehrens, X. H. T., Lehnart, S. E., Reiken, S. R., & Marks, A. R. (2004) · Circulation Research · doi:10.1161/01.res.0000125626.33738.e2 · Cited by 623
Self-citationCalmodulin kinase II inhibition protects against structural heart disease
Zhang, R., Khoo, M. S. C., Wu, Y., Yang, Y., Grueter, C. E., Ni, G., Price, E. E., Thiel, W., Guatimosim, S., Song, L.-S., et al. (2005) · Nature Medicine · doi:10.1038/nm1215 · Cited by 579
Self-citationZhang, T., Maier, L. S., Dalton, N. D., Miyamoto, S., Ross, J., Bers, D. M., & Brown, J. H. (2003) · Circulation Research · doi:10.1161/01.res.0000069686.31472.c5 · Cited by 556
Self-citationCa2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels
Wagner, S., Dybkova, N., Rasenack, E. C. L., Jacobshagen, C., Fabritz, L., Kirchhof, P., Maier, S. K. G., Zhang, T., Hasenfuss, G., Brown, J. H., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26620 · Cited by 553
Self-citationProtection from Cardiac Arrhythmia Through Ryanodine Receptor-Stabilizing Protein Calstabin2
Wehrens, X. H. T., Lehnart, S. E., Reiken, S. R., Deng, S.-X., Vest, J. A., Cervantes, D., Coromilas, J., Landry, D. W., & Marks, A. R. (2004) · Science · doi:10.1126/science.1094301 · Cited by 480
Self-citationMaier, L. S., Zhang, T., Chen, L., DeSantiago, J., Brown, J. H., & Bers, D. M. (2003) · Circulation Research · doi:10.1161/01.res.0000069685.20258.f1 · Cited by 433
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Cited by
Voigt, N., Li, N., Wang, Q., Wang, W., Trafford, A. W., Abu-Taha, I., Sun, Q., Wieland, T., Ravens, U., Nattel, S., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.067306 · Cited by 624
Self-citationCaMKII in myocardial hypertrophy and heart failure
Anderson, M. E., Brown, J. H., & Bers, D. M. (2011) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.01.012 · Cited by 465
Self-citationSignaling effectors underlying pathologic growth and remodeling of the heart
van Berlo, J. H., Maillet, M., & Molkentin, J. D. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62839 · Cited by 445
Mechanisms of Altered Ca 2+ Handling in Heart Failure
Luo, M., & Anderson, M. E. (2013) · Circulation Research · doi:10.1161/circresaha.113.301651 · Cited by 357
Self-citationCircadian rhythms govern cardiac repolarization and arrhythmogenesis
Jeyaraj, D., Haldar, S. M., Wan, X., McCauley, M. D., Ripperger, J. A., Hu, K., Lu, Y., Eapen, B. L., Sharma, N., Ficker, E., et al. (2012) · Nature · doi:10.1038/nature10852 · Cited by 343
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Metadata
- Authors
- van Oort, R. J., McCauley, M. D., Dixit, S. S., Pereira, L., Yang, Y., Respress, J. L., Wang, Q., De Almeida, A. C., Skapura, D. G., Anderson, M. E., Bers, D. M., & Wehrens, X. H. T.
- Venue
- Circulation
- Published
- 2010-12-21
- Volume
- 122
- Issue
- 25
- Pages
- 2669-2679
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2155116390
- Cited by
- 310
- References
- 36
- FWCI
- 14.92
- Type
- journal article
- Language
- en
- Open access
- bronze
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- van Oort, R. J., McCauley, M. D., Dixit, S. S., Pereira, L., Yang, Y., Respress, J. L., Wang, Q., De Almeida, A. C., Skapura, D. G., Anderson, M. E., Bers, D. M., & Wehrens, X. H. T. (2010). Ryanodine Receptor Phosphorylation by Calcium/Calmodulin-Dependent Protein Kinase II Promotes Life-Threatening Ventricular Arrhythmias in Mice With Heart Failure. Circulation. https://doi.org/10.1161/circulationaha.110.982298
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