NDLI: Role of CaMKII in cardiac arrhythmias

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Role of CaMKII in cardiac arrhythmias

Content Provider	PubMed Central
Author	Hund, Thomas J. Mohler, Peter J.
Copyright Year	2014
Abstract	Protein phosphorylation is a central mechanism in vertebrates for the regulation of signaling. With regard to the cardiovascular system, phosphorylation of myocyte targets is critical for the regulation of excitation contraction coupling, metabolism, intracellular calcium regulation, mitochondrial activity, transcriptional regulation, and cytoskeletal dynamics. In fact, pathways that tune protein kinase signaling have been a mainstay for cardiovascular therapies for the past 60 years. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase with numerous roles in human physiology. Dysfunction in CaMKII-based signaling has been linked with a host of cardiovascular phenotypes including heart failure and arrhythmia, and CaMKII levels are elevated in human and animal disease models of heart disease. While nearly a decade has been invested in targeting CaMKII for the treatment of heart failure and arrhythmia phenotypes, to date, approaches to target the molecule for antiarrhythmic benefit have been unsuccessful for reasons that are still not entirely clear, although (1) lack of compound specificity and (2) the multitude of downstream targets are likely contributing factors. This review will provide an update on current pathways regulated by CaMKII with the goal of illustrating potential upstream regulatory mechanisms and downstream targets that may be modulated for the prevention of cardiac electrical defects. While the review will cover multiple aspects of CaMKII dysfunction in cardiovascular disease, we have given special attention to the potential of CaMKII-associated late Na+ current as a novel therapeutic target for cardiac arrhythmia.
Related Links	http://dx.doi.org/10.1016/j.tcm.2014.12.001
Ending Page	397
Page Count	6
Starting Page	392
File Format	PDF
ISSN	10501738
e-ISSN	18732615
Journal	Trends in cardiovascular medicine
Issue Number	5
Volume Number	25
Language	English
Publisher Date	2015-07-01
Access Restriction	Open
Subject Keyword	Cardiology and Cardiovascular Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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