Cardiology Letters 2023, 32(4):271-280

The role of calcium/calmodulin-dependent protein kinase 2 in serious cardiovascular pathologies and its clinical potential

Rajtík T^{1, 2}

¹ Katedry farmakológie a toxikológie, Farmaceutická fakulta, Univerzita Komenského v Bratislave

² Ústav pre výskum srdca, Centrum experimentálnej medicíny, Slovenská Akadémia Vied, Bratislava, Slovenská republika

Cardiac pathologies such as arrhythmias, myocardial infarction or chronic heart failure are among the significant epidemiological, therapeutic and financial challenges of our time but, despite this, new pharmacotherapeutic tools for their management are still insufficient. Calcium plays a critical role in the pathophysiology of heart, as it mediates the excitationcontraction and excitation-transcriptional coupling in myocytes. Its dysregulation leads to the occurrence of many serious phenotypes of cell damage, from contractile dysfunction to cell death or pathological remodeling, and subsequently dysfunction of the heart as an organ. Despite, or precisely because of this ubiquitous nature of calcium, there are only few practically used groups of drugs in the therapy, such as L-type calcium channel antagonists or calcium sensitizers. Calcium/calmodulin-dependent protein kinase 2 (CaMKII) plays a pivotal role in the regulation of calcium turnover, regulating its influx into the cytoplasm, its removal into the sarcoendoplasmic reticulum, as well as calcium-dependent transcription and metabolism. This is precisely why its pharmacological modulation or inhibition is an interesting research goal, especially in the context of the lack of new treatment procedures in the above-mentioned serious cardiac pathologies, and may represent an important new step in their treatment. The aim of this review article is to provide an insight into its action in the heart, the possibilities of its regulation at the level of post-translational modifications and experimental or clinical possibilities in the future therapy of serious cardiac pathologies.

Keywords: calcium; CaMKII; ischemia, reperfusion; arrhythmias; heart failure

Published: April 1, 2023  Show citation