Calcium Signalling in Heart and Vessels: Role of Calmodulin and Downstream Calmodulin-Dependent Protein Kinases

Int J Mol Sci. 2022 Dec 17;23(24):16139. doi: 10.3390/ijms232416139.

Abstract

Cardiovascular disease is the major cause of death worldwide. The success of medication and other preventive measures introduced in the last century have not yet halted the epidemic of cardiovascular disease. Although the molecular mechanisms of the pathophysiology of the heart and vessels have been extensively studied, the burden of ischemic cardiovascular conditions has risen to become a top cause of morbidity and mortality. Calcium has important functions in the cardiovascular system. Calcium is involved in the mechanism of excitation-contraction coupling that regulates numerous events, ranging from the production of action potentials to the contraction of cardiomyocytes and vascular smooth muscle cells. Both in the heart and vessels, the rise of intracellular calcium is sensed by calmodulin, a protein that regulates and activates downstream kinases involved in regulating calcium signalling. Among them is the calcium calmodulin kinase family, which is involved in the regulation of cardiac functions. In this review, we present the current literature regarding the role of calcium/calmodulin pathways in the heart and vessels with the aim to summarize our mechanistic understanding of this process and to open novel avenues for research.

Keywords: calcium calmodulin dependent protein kinases; calcium signalling; calmodulin; cardiovascular disease.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Calmodulin* / metabolism
  • Cardiovascular Diseases* / metabolism
  • Humans
  • Myocytes, Cardiac / metabolism

Substances

  • Calmodulin
  • Calcium
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2

Grants and funding

This work was in part funded by the European Union’s Horizon 2020 research and innovation programmes under the Marie Sklodowska-Curie grant agreement No 764474.