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

Research output: Contribution to journalReview article

165 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)769-785
Number of pages17
JournalPflugers Archiv European Journal of Physiology
Volume456
Issue number5
DOIs
StatePublished - Aug 1 2008

Fingerprint

Calcium Signaling
Vascular Diseases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Smooth Muscle
Muscle
Calcium
Phenotype
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Pumps
Muscle Contraction
Protein Isoforms
Electric potential
Switches
Cell Proliferation
Cell signaling
Transient Receptor Potential Channels
Drug therapy
Calcium-Calmodulin-Dependent Protein Kinase Type 2

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

House, Suzanne J. ; Potier, Marie ; Bisaillon, Jonathan ; Singer, Harold A. ; Trebak, Mohamed. / The non-excitable smooth muscle : Calcium signaling and phenotypic switching during vascular disease. In: Pflugers Archiv European Journal of Physiology. 2008 ; Vol. 456, No. 5. pp. 769-785.
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The non-excitable smooth muscle : Calcium signaling and phenotypic switching during vascular disease. / House, Suzanne J.; Potier, Marie; Bisaillon, Jonathan; Singer, Harold A.; Trebak, Mohamed.

In: Pflugers Archiv European Journal of Physiology, Vol. 456, No. 5, 01.08.2008, p. 769-785.

Research output: Contribution to journalReview article

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T1 - The non-excitable smooth muscle

T2 - Calcium signaling and phenotypic switching during vascular disease

AU - House, Suzanne J.

AU - Potier, Marie

AU - Bisaillon, Jonathan

AU - Singer, Harold A.

AU - Trebak, Mohamed

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N2 - 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.

AB - 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.

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