Abstract
Transient receptor potential canonical 5 (TRPC5) is a calcium-permeable channel first detected in the central nervous system but recently appreciated to have a broader expression profile, including localisation to heart and blood vessels. To explore the potential relevance of the channel we screened for effects of lipids with established importance as cardiovascular signals. We find heterologously-expressed TRPC5 calcium channel can be activated by sphingosine-1-phosphate (S1P). As S1P has important roles in the cardiovascular system and complex effects on vascular smooth muscle cell migration, we were motivated to investigate the functional role of TRPC5 in S1P responses. Using saphenous vein obtained during open-heart surgery, we first confirm the expression of TRPC5 in vascular smooth muscle. E3-targeted antibody to TRPC5 (Xu et al, 2005, Nat Biotech 1289,1293-) inhibits S1P-evoked smooth muscle cell migration. Using Amaxa primary cell transfection we delivered dominant negative TRPC5 to smooth muscle cells. Strikingly we find the effect of S1P on cell-migration is suppressed. These data suggest TRPC5 has a previously unappreciated sensitivity to S1P that plays a role in the vascular injury response. Supported by the Wellcome Trust (UK), BBSRC (UK), BHF(UK), Daiwa Foundation and Nakatomi Health Foundation International Exchange Programme.
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