AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (October 9, 2003). doi:10.1152/ajpheart.00826.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
286/3/H1015    most recent
00826.2003v1
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 Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pocock, T. M.
Right arrow Articles by Bates, D. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pocock, T. M.
Right arrow Articles by Bates, D. O.
Submitted on August 27, 2003
Accepted on October 3, 2003

Evidence of a role for TRPC channels in vascular endothelial growth factor mediated increased vascular permeability in vivo

T. M. Pocock1, R. R. Foster1, and D. O. Bates1*

1 Microvascular Research Laboratories, Department of Physiology, University of Bristol, Bristol, United Kingdom

* To whom correspondence should be addressed. E-mail: Dave.Bates{at}bris.ac.uk.

Vascular endothelial growth factor (VEGF) increases vascular permeability by stimulating endothelial calcium influx. Here we provide evidence that links VEGF mediated increased permeability and endothelial calcium concentration ([Ca2+]i) with diacylglycerol (DAG) mediated activation of the transient receptor potential channels (TRPCs). We used the Landis-Michel technique to measure changes in hydraulic conductivity (Lp) and fluorescence photometry to measure changes in [Ca2+]i in individually perfused Rana mesenteric microvessels in vivo, and transfected non-endothelial cells in vitro. The membrane-permeant DAG analogue, 1-oleoyl-2-acetyl-sn-glycerol (OAG; 100µM), known to increase calcium influx through TRPC channels, transiently increased Lp 3.8 ± 1.2 fold (from 1.6 ± 0.8 to 9.8 ± 2.7 x 10-7 cm.s-1.cmH2O-1, p<0.0001; n=18). Protein kinase C inhibition by bisindolylmaleimide (BIM; 1µM) did not affect the OAG-induced increases in Lp. OAG also significantly increased microvascular endothelial [Ca2+]i in vivo (n=13; p<0.0001), which again was not sensitive to PKC inhibition. VEGF induced a transient increase in [Ca2+]i in human embryonic kidney cells (HEK293) co-transfected with VEGFR-2 and TRPC6, but not with control, VEGFR-2 or TRPC6 expression vector alone (p<0.01, n=9). Flufenamic acid, which has been shown to enhance TRPC6 activity, but inhibit TRPC3 and 7, enhanced the VEGF mediated increase in Lp in approximately half the vessels tested, but inhibited the response in the other half. These data provide evidence consistent with the hypothesis that VEGF increases vascular permeability through DAG mediated calcium entry through TRPC channels. Although the exact identities of the TRPC channels remain to be confirmed, TRPC6 appears to be a likely candidate in approximately half the vessels.




This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
P. Chaudhuri, S. M. Colles, M. Bhat, D. R. Van Wagoner, L. Birnbaumer, and L. M. Graham
Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement
Mol. Biol. Cell, August 1, 2008; 19(8): 3203 - 3211.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
I. N. Gavrilovskaya, E. E. Gorbunova, N. A. Mackow, and E. R. Mackow
Hantaviruses Direct Endothelial Cell Permeability by Sensitizing Cells to the Vascular Permeability Factor VEGF, while Angiopoietin 1 and Sphingosine 1-Phosphate Inhibit Hantavirus-Directed Permeability
J. Virol., June 15, 2008; 82(12): 5797 - 5806.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
H.-W. Cheng, A.F. James, R.R. Foster, J.C. Hancox, and D.O. Bates
VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1768 - 1776.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
D. Mehta and A. B. Malik
Signaling Mechanisms Regulating Endothelial Permeability
Physiol Rev, January 1, 2006; 86(1): 279 - 367.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. F. Alvarez, J. A. King, and M. I. Townsley
Resistance to Store Depletion-induced Endothelial Injury in Rat Lung after Chronic Heart Failure
Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1153 - 1160.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
X. Yao and C. J. Garland
Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels
Circ. Res., October 28, 2005; 97(9): 853 - 863.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
D. Jho, D. Mehta, G. Ahmmed, X.-P. Gao, C. Tiruppathi, M. Broman, and A. B. Malik
Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca2 Influx
Circ. Res., June 24, 2005; 96(12): 1282 - 1290.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
C. A. Glass, T. M. Pocock, F. E. Curry, and D. O. Bates
Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo
J. Physiol., May 1, 2005; 564(3): 817 - 827.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.