Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Pflugers Arch. 2008 Aug;456(5):769-85. doi: 10.1007/s00424-008-0491-8. Epub 2008 Mar 26.

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

Author information

  • 1The Center for Cardiovascular Sciences, Albany Medical College, 47, New Scotland Avenue, MC-8, Albany, NY, 12208, USA.


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

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (1)Free text

Fig. 1
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for Springer Icon for PubMed Central
    Loading ...
    Write to the Help Desk