Pflügers Archiv - European Journal of Physiology

, Volume 456, Issue 5, pp 769–785

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

  • Suzanne J. House
  • Marie Potier
  • Jonathan Bisaillon
  • Harold A. Singer
  • Mohamed Trebak
Invited Review


Calcium (Ca2+) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca2+ permeable channels, Ca2+ pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca2+ levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca2+ signaling pathways that regulate VSMC contraction are the plasma membrane voltage-operated Ca2+ channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca2+ release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca2+ signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca2+ channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca2+ release channels, pumps and Ca2+-activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform 2a pump and reciprocally regulate isoforms of the ca2+/calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca2+ signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca2+ signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.


Vascular smooth muscle cell proliferation Phenotypic switching  Ca2+ signaling Canonical transient receptor potential channels L-type and T-type voltage-dependent Ca2+ channels Membrane potential Potassium channels Ca2+/calmodulin-dependent protein kinase II (CaMKII) 


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Suzanne J. House
    • 1
  • Marie Potier
    • 1
  • Jonathan Bisaillon
    • 1
  • Harold A. Singer
    • 1
  • Mohamed Trebak
    • 1
  1. 1.The Center for Cardiovascular SciencesAlbany Medical CollegeAlbanyUSA

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