Cardiac calmodulin kinase

A potential target for drug design

T. Bányász, N. Szentandrássy, A. Tóth, P. Nánási, J. Magyar, Y. Chen-Izu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Therapeutic strategy for cardiac arrhythmias has undergone a remarkable change during the last decades. Currently implantable cardioverter defibrillator therapy is considered to be the most effective therapeutic method to treat malignant arrhythmias. Some even argue that there is no room for antiarrhythmic drug therapy in the age of implantable cardioverter defibrillators. However, in clinical practice, antiarrhythmic drug therapies are frequently needed, because implantable cardioverter defibrillators are not effective in certain types of arrhythmias (i.e. premature ventricular beats or atrial fibrillation). Furthermore, given the staggering cost of device therapy, it is economically imperative to develop alternative effective treatments. Cardiac ion channels are the target of a number of current treatment strategies, but therapies based on ion channel blockers only resulted in moderate success. Furthermore, these drugs are associated with an increased risk of proarrhythmia, systemic toxicity, and increased defibrillation threshold. In many cases, certain ion channel blockers were found to increase mortality. Other drug classes such as β-blockers, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and statins appear to have proven efficacy for reducing cardiac mortality. These facts forced researchers to shift the focus of their research to molecular targets that act upstream of ion channels. One of these potential targets is calcium/calmodulin-dependent kinase II (CaMKII). Several lines of evidence converge to suggest that CaMKII inhibition may provide an effective treatment strategy for heart diseases. (1) Recent studies have elucidated that CaMKII plays a key role in modulating cardiac function and regulating hypertrophy development. (2) CaMKII activity has been found elevated in the failing hearts from human patients and animal models. (3) Inhibition of CaMKII activity has been shown to mitigate hypertrophy, prevent functional remodeling and reduce arrhythmogenic activity. In this review, we will discuss the structural and functional properties of CaMKII, the modes of its activation and the functional consequences of CaMKII activity on ion channels.

Original languageEnglish
Pages (from-to)3707-3713
Number of pages7
JournalCurrent Medicinal Chemistry
Volume18
Issue number24
DOIs
Publication statusPublished - Aug 2011

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinases
Drug Design
Calmodulin
Phosphotransferases
Ion Channels
Implantable cardioverter defibrillators
Pharmaceutical Preparations
Implantable Defibrillators
Drug therapy
Cardiac Arrhythmias
Anti-Arrhythmia Agents
Therapeutics
Hypertrophy
Mineralocorticoid Receptor Antagonists
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Drug Therapy
Ventricular Premature Complexes
Mortality
Angiotensin-Converting Enzyme Inhibitors
Ventricular Fibrillation

Keywords

  • Arrhythmia
  • Calmodulin kinase
  • Heart
  • Hypertrophy
  • Ion channels

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Cardiac calmodulin kinase : A potential target for drug design. / Bányász, T.; Szentandrássy, N.; Tóth, A.; Nánási, P.; Magyar, J.; Chen-Izu, Y.

In: Current Medicinal Chemistry, Vol. 18, No. 24, 08.2011, p. 3707-3713.

Research output: Contribution to journalArticle

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