Skip Navigation


Bioscience Horizons Advance Access originally published online on April 23, 2008
Bioscience Horizons 2008 1(2):92-97; doi:10.1093/biohorizons/hzn013
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
1/2/92    most recent
hzn013v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Fahy, S.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Fahy, S.
Related Collections
Right arrow Biomedical Science
Right arrow Cell Biology
Right arrow Pharmacology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sphingosine-1-phosphate activation of TRPC5 in vascular smooth muscle cells

Samantha Fahy

University of Leeds, Leeds, UK

Supervisor: Prof. David Beech, Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK.


  Abstract

Calcium signalling is a complex and diverse system utilized in many cellular processes and in the transmission of cellular information. A number of transient receptor potential (TRP) proteins have been identified in humans and other mammals; these proteins are implicated as having a role in calcium signalling. TRPC5 is a member of this protein family which combines with TRPC1 to form non-selective cation channels in human saphenous vein cells, a type of smooth muscle cell. The exact function of TRPC5 remains elusive, however, it can be activated by sphingosine-1-phosphate (S1P), an endogenous signalling phospholipid involved in SMC migration.

The aim of these experiments was to investigate the effects of S1P on the intracellular calcium concentration, [Ca2+]i, in HSV cells, utilizing dominant-negative (DN)-TRPC5 transfected cells to establish the role played by TRPC5 in this response. A secondary aim was to establish the effect of SMC migration on the above response parameters to S1P using the HSV scratch assay, where a ~2 mm line of cells was scraped away from the surface of a glass cover slip and the remaining cells incubated for 24 h.

Concurrent with the literature, S1P evoked a significant response in HSV cells (n=23; P=0.001). The baseline was significantly lower in the DN-TRPC5 cells compared with the control cells (P<0.001), and the maximum response in the DN-TRPC5 transfected HSV cells reached only 60% of the maximum response in control cells. This suggested that TRPC5 was involved with maintaining basal [Ca2+]i levels and indicated the proportion of the response for which TRPC5 was responsible.

The response to S1P was significantly larger in migrated (n=7) compared with static (n=11) HSV cells (P=<0.001) and this response was delayed by ~2.3 min; the baseline was also higher in the latter group. This suggested a functional change in the cell following migration that may have been attributable to TRPC5, for example, channel up-regulation.

In conclusion, TRPC5-like channels are responsible for a proportion of the S1P response and are implicated in SMC migration. This highlights potential pharmacological targets for the treatment of atherosclerosis, neointimal hyperplasia and coronary heart disease.

Key words: TRPC5, S1P, saphenous, Fura-2, calcium

Submitted on 17 January 2008; accepted on 11 February 2008


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.