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The Role of CaM Kinase II in Cardiac Function in Health and Disease

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Cardiac Adaptations

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 4))

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Abstract

Ca2+-calmodulin-dependent protein kinase II (CaMKII) has emerged as a critical molecule involved in the regulation of cell processes that are dependent on calcium, including excitation–contraction coupling (ECC), cell growth, and death. In addition to a generally accepted signaling pathway through beta-adrenergic receptors (ARs), oxidative stress has been suggested to promote CaMKII activation. Since many cardiac diseases, including those characterized by a phenomenon called as ischemia/reperfusion injury (IRI), are associated with oxidative stress, CaMKII is likely to be a crucial molecule underlying the phenotypes of this cardiac injury. In contrast, there is also evidence that CaMKII activation leading to phosphorylation of phospholamban and the subsequent decrease of calcium overload is important for attenuation of post-ischemic cardiac contracture, indicating that CaMKII may act as a double-edged sword depending on the actual conditions. In addition, CaMKII over-activation has been shown to destabilize the action potential and trigger early and delayed afterdepolarizations promoting arrhythmias. Experimental studies from our laboratory have revealed that CaMKII inhibition does not protect the heart against all types of IRI-induced ventricular arrhythmias, but it is capable to reduce the occurrence of the most life-threatening tachyarrhythmias. Moreover, the CaMKII inhibition appears to reduce oxidative stress and thus to increase the viability of cardiomyocytes upon IRI. In this manuscript, a dual role of CaMKII in IRI is reviewed and beneficial effects of the CaMKII inhibition are discussed with studies that have shown the opposite results. We conclude that CaMKII activation either inhibition should be carefully considered in effort to mitigate cardiac IRI-induced injury.

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Acknowledgments

The research in this article was supported by a grant from Slovak Scientific Grant Agency (VEGA) 1/0638/12 and 2/0054/11, APVV-0523-10 and APVV-0102-11.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Comenius University, Odbojarov 10, 832 32, Bratislava, Slovak Republic

    Adriana Adameova, Adrian Szobi & Tomas Rajtik

  2. Institute for Heart Research, Slovak Academy of Sciences and Centre of Excellence NOREG SAS, Bratislava, Slovak Republic

    Slavka Carnicka & Tanya Ravingerova

Authors
  1. Adriana Adameova
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  2. Adrian Szobi
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  3. Slavka Carnicka
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  4. Tanya Ravingerova
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  5. Tomas Rajtik
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Correspondence to Adriana Adameova .

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Editors and Affiliations

  1. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

  2. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Adameova, A., Szobi, A., Carnicka, S., Ravingerova, T., Rajtik, T. (2013). The Role of CaM Kinase II in Cardiac Function in Health and Disease. In: Ostadal, B., Dhalla, N. (eds) Cardiac Adaptations. Advances in Biochemistry in Health and Disease, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5203-4_24

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