Advanced

Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry.

Bergdahl, Andreas LU ; Gomez, Maria LU ; Wihlborg, Anna-Karin LU ; Erlinge, David LU ; Eyjolfson, Atli; Xu, Shang-Zhong; Beech, David J.; Dreja, Karl LU and Hellstrand, Per LU (2005) In American Journal of Physiology: Cell Physiology 288(4). p.872-880
Abstract
Loss of the smooth muscle contractile phenotype is critical in atherosclerosis and in restenosis after angioplasty, but its early signals are incompletely understood. In this study, we have explored the role of transient receptor potential canonical (TRPC) proteins, which have been suggested to mediate store-operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ culture is preserved for several days, whereas SOCE is increased. In correlation with this increase is that nifedipine-insensitive whole cell current, activated by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold increased in cells isolated after organ... (More)
Loss of the smooth muscle contractile phenotype is critical in atherosclerosis and in restenosis after angioplasty, but its early signals are incompletely understood. In this study, we have explored the role of transient receptor potential canonical (TRPC) proteins, which have been suggested to mediate store-operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ culture is preserved for several days, whereas SOCE is increased. In correlation with this increase is that nifedipine-insensitive whole cell current, activated by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold increased in cells isolated after organ culture, whereas TRPC3 was decreased. Immunofluorescent staining and/or Western blotting of arteries and isolated cells showed upregulation of TRPC1 and TRPC6 proteins during organ culture. In intact arteries, TRPC4 expression correlated with the amount of endothelium present. Ca2+ addition after store depletion caused a contraction in cultured, but not in freshly dissected, arteries. A polyclonal TRPC1 antibody directed against an extracellular epitope inhibited this contraction by approximately 50%. To investigate the basis of the TRPC upregulation and assess its possible clinical significance, segments of human internal mammary artery were organ cultured for 24 h and then exposed to balloon dilatation in vitro, followed by further culturing for up to 48 h. After dilatation, TRPC1 and TRPC6 mRNA were progressively increased compared with undilated control segments. The results of this study indicate that vascular injury enhances plasticity in TRPC expression, that TRPC expression correlates with cellular Ca2+ handling, and that TRPC1 is a subunit of upregulated store-operated Ca2+ channels. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
organ culture, angioplasty, ion channels, differentiation
in
American Journal of Physiology: Cell Physiology
volume
288
issue
4
pages
872 - 880
publisher
American Physiological Society
external identifiers
  • wos:000227543300011
  • pmid:15561760
  • scopus:15444370972
ISSN
1522-1563
DOI
10.1152/ajpcell.00334.2004
language
English
LU publication?
yes
id
c976cd39-2727-4248-8759-e543eae52935 (old id 130687)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15561760&dopt=Abstract
date added to LUP
2007-07-10 11:57:53
date last changed
2017-10-01 04:54:01
@article{c976cd39-2727-4248-8759-e543eae52935,
  abstract     = {Loss of the smooth muscle contractile phenotype is critical in atherosclerosis and in restenosis after angioplasty, but its early signals are incompletely understood. In this study, we have explored the role of transient receptor potential canonical (TRPC) proteins, which have been suggested to mediate store-operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ culture is preserved for several days, whereas SOCE is increased. In correlation with this increase is that nifedipine-insensitive whole cell current, activated by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold increased in cells isolated after organ culture, whereas TRPC3 was decreased. Immunofluorescent staining and/or Western blotting of arteries and isolated cells showed upregulation of TRPC1 and TRPC6 proteins during organ culture. In intact arteries, TRPC4 expression correlated with the amount of endothelium present. Ca2+ addition after store depletion caused a contraction in cultured, but not in freshly dissected, arteries. A polyclonal TRPC1 antibody directed against an extracellular epitope inhibited this contraction by approximately 50%. To investigate the basis of the TRPC upregulation and assess its possible clinical significance, segments of human internal mammary artery were organ cultured for 24 h and then exposed to balloon dilatation in vitro, followed by further culturing for up to 48 h. After dilatation, TRPC1 and TRPC6 mRNA were progressively increased compared with undilated control segments. The results of this study indicate that vascular injury enhances plasticity in TRPC expression, that TRPC expression correlates with cellular Ca2+ handling, and that TRPC1 is a subunit of upregulated store-operated Ca2+ channels.},
  author       = {Bergdahl, Andreas and Gomez, Maria and Wihlborg, Anna-Karin and Erlinge, David and Eyjolfson, Atli and Xu, Shang-Zhong and Beech, David J. and Dreja, Karl and Hellstrand, Per},
  issn         = {1522-1563},
  keyword      = {organ culture,angioplasty,ion channels,differentiation},
  language     = {eng},
  number       = {4},
  pages        = {872--880},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Cell Physiology},
  title        = {Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry.},
  url          = {http://dx.doi.org/10.1152/ajpcell.00334.2004},
  volume       = {288},
  year         = {2005},
}