Intracellular Ca2+ Signalling and Phenotype of Vascular Smooth Muscle Cells

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 Ca2+ signalling, which is a consequence of difference in expression of Ca2+ transport proteins. Contractile VSMCs express Ca2+ transporters, including voltage-gated L-type Ca2+ channels and SERCA2a pump, which maintain low resting cytosolic Ca2+ and allow dynamic changes of Ca2+ in the spatial and temporal domain, while non-contractile VSMCs have significantly reduced voltage dependence of Ca2+ 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, Ca2+-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 Ca2+ signalling. Thus, different Ca2+ transport proteins not only control averaged intracellular Ca2+ but also through their differences in the character of the Ca2+ signal modulate the activity of transcription factors and thus initiate phenotype switch. The essential stimuli for phenotype switch are unknown, but intracellular Ca2+ is an important second messenger in the cell transcription programme. This article reviews the relationship between intracellular Ca2+ signalling and VSMC phenotype.