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Intracellular Ca 2+ Signalling and Phenotype of Vascular Smooth Muscle Cells
Author(s) -
Matchkov Vladimir V.,
Kudryavtseva Olga,
Aalkjaer Christian
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00818.x
Subject(s) - intracellular , phenotype , microbiology and biotechnology , vascular smooth muscle , transcription factor , biology , cytosol , calcium signaling , second messenger system , signal transduction , gene , endocrinology , biochemistry , smooth muscle , enzyme
Vascular smooth muscle cells (VSMCs) express considerable plasticity in their phenotype and even can change their phenotype in vivo depending on the functional demand. In addition to contractile phenotype, VSMCs can be proliferative, migrating and/or synthetic. Importantly, contractile and non‐contractile phenotypes differ significantly in their intracellular Ca 2+ signalling, which is a consequence of difference in expression of Ca 2+ transport proteins. Contractile VSMCs express Ca 2+ transporters, including voltage‐gated L‐type Ca 2+ channels and SERCA2a pump, which maintain low resting cytosolic Ca 2+ and allow dynamic changes of Ca 2+ in the spatial and temporal domain, while non‐contractile VSMCs have significantly reduced voltage dependence of Ca 2+ entry. These changes associated with phenotypic switch are consequences of changes in gene expression programmes, where the expression of phenotype‐specific proteins and other proteins is suppressed. Importantly, Ca 2+ ‐sensitive transcription factors, including serum response factor, cAMP response element–binding protein and nuclear factor of activated T lymphocytes, which are important for this phenotype switch, can be activated by different types of Ca 2+ signalling. Thus, different Ca 2+ transport proteins not only control averaged intracellular Ca 2+ but also through their differences in the character of the Ca 2+ signal modulate the activity of transcription factors and thus initiate phenotype switch. The essential stimuli for phenotype switch are unknown, but intracellular Ca 2+ is an important second messenger in the cell transcription programme. This article reviews the relationship between intracellular Ca 2+ signalling and VSMC phenotype.