Journal article
Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias
Circulation research, Vol.110(12), pp.1661-1677
06/08/2012
DOI: 10.1161/CIRCRESAHA.111.243956
PMCID: PMC3789535
PMID: 22679140
Abstract
Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the past decade supports a view that activation of the multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca(2+) or oxidation, upstream signals with the capacity to transition CaMKII into a Ca(2+) and calmodulin-independent constitutively active enzyme. Constitutively active CaMKII appears poised to participate in disease pathways by catalyzing the phosphorylation of classes of protein targets important for excitation-contraction coupling and cell survival, including ion channels and Ca(2+) homeostatic proteins, and transcription factors that drive hypertrophic and inflammatory gene expression. This rich diversity of downstream targets helps to explain the potential for CaMKII to simultaneously affect mechanical and electrical properties of heart muscle cells. Proof-of-concept studies from a growing number of investigators show that CaMKII inhibition is beneficial for improving myocardial performance and for reducing arrhythmias. We review the molecular physiology of CaMKII and discuss CaMKII actions at key cellular targets and results of animal models of myocardial hypertrophy, dysfunction, and arrhythmias that suggest CaMKII inhibition may benefit myocardial function while reducing arrhythmias.
Details
- Title: Subtitle
- Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias
- Creators
- Paari Dominic Swaminathan - Roy J. and Lucille A. Carver College of MedicineAnil Purohit - University of IowaThomas J Hund - The Ohio State UniversityMark E Anderson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.110(12), pp.1661-1677
- DOI
- 10.1161/CIRCRESAHA.111.243956
- PMID
- 22679140
- PMCID
- PMC3789535
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Grant note
- R01 HL 096652 / NHLBI NIH HHS R01 HL 079031 / NHLBI NIH HHS R00 HL 096805 / NHLBI NIH HHS R01 HL 070250 / NHLBI NIH HHS R01 HL113001 / NHLBI NIH HHS R01 HL079031 / NHLBI NIH HHS R01 HL070250 / NHLBI NIH HHS R01 HL096652 / NHLBI NIH HHS R01 HL 113001 / NHLBI NIH HHS R00 HL096805 / NHLBI NIH HHS
- Language
- English
- Date published
- 06/08/2012
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984366293002771
Metrics
16 Record Views