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Vascular Ion Channels in Physiology and Disease pp 275–294Cite as

TRPC and Orai Channels in Store-Operated Calcium Entry and Vascular Remodelling

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Abstract

In this article we address ion channels formed by Transient Receptor Potential Canonical (TRPC) proteins and Orai proteins and the phenomenon of store-operated Ca2+ entry (SOCE) as they relate to vascular remodelling and two dominant cell types in this biology, the vascular smooth muscle cells and the endothelial cells. Emphasis is placed on studies published by our group but there is also general introduction for non-experts, critical evaluation, and debate of current concepts, controversies, and future perspectives. Overall we believe that this is an interesting and important area of biology that still raises unsolved questions and substantial technical challenges if full understanding is to be achieved. It is our opinion that within these mechanisms there are important targets for the discovery and development of novel therapeutic agents to address key unsolved disease challenges in the cardiovascular, cancer and many other fields.

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References

  1. McKeown L, et al. Platelet-derived growth factor maintains stored calcium through a nonclustering Orai1 mechanism but evokes clustering if the endoplasmic reticulum is stressed by store depletion. Circ Res. 2012;111:66–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004;84:767–801.

    Article  CAS  PubMed  Google Scholar 

  3. Beech DJ. Ion channel switching and activation in smooth-muscle cells of occlusive vascular diseases. Biochem Soc Trans. 2007;35:890–4.

    Article  CAS  PubMed  Google Scholar 

  4. Beech DJ. Characteristics of transient receptor potential canonical calcium-permeable channels and their relevance to vascular physiology and disease. Circ J. 2013;77:570–9.

    Article  CAS  PubMed  Google Scholar 

  5. Abramowitz J, Birnbaumer L. Physiology and pathophysiology of canonical transient receptor potential channels. FASEB J. 2009;23:297–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Feske S. ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond. Immunol Rev. 2009;231:189–209.

    Article  CAS  PubMed  Google Scholar 

  7. Feske S, et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006;441:179–85.

    Article  CAS  PubMed  Google Scholar 

  8. Prakriya M, et al. Orai1 is an essential pore subunit of the CRAC channel. Nature. 2006;443:230–3.

    Article  CAS  PubMed  Google Scholar 

  9. McNally BA, Somasundaram A, Yamashita M, Prakriya M. Gated regulation of CRAC channel ion selectivity by STIM1. Nature. 2012;482:241–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang B, Gwozdz T, Dutko-Gwozdz J, Bolotina VM. Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells. Am J Physiol. 2012;302:C748–56.

    Article  CAS  Google Scholar 

  11. Shuttleworth TJ. Orai channels—new insights, new ideas. J Physiol. 2012;590:4155–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Philipp S, et al. A novel capacitative calcium entry channel expressed in excitable cells. EMBO J. 1998;17:4274–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Beech DJ. TRPC1: store-operated channel and more. Pflugers Arch. 2005;451:53–60.

    Article  CAS  PubMed  Google Scholar 

  14. Beech DJ. Orai1 calcium channels in the vasculature. Pflugers Arch. 2012;463:635–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Damann N, Voets T, Nilius B. TRPs in our senses. Curr Biol. 2008;18:R880–9.

    Article  CAS  PubMed  Google Scholar 

  16. Bon RS, Beech DJ. In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels—mirage or pot of gold? Br J Pharmacol. 2013;170:459–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liao M, Cao E, Julius D, Cheng Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature. 2013;504:107–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Freichel M, et al. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice. Nat Cell Biol. 2001;3:121–7.

    Article  CAS  PubMed  Google Scholar 

  19. Zeng F, et al. Human TRPC5 channel activated by a multiplicity of signals in a single cell. J Physiol. 2004;559:739–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Beech DJ. Harmony and discord in endothelial calcium entry. Circ Res. 2009;104:e22–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Xu SZ, et al. A sphingosine-1-phosphate-activated calcium channel controlling vascular smooth muscle cell motility. Circ Res. 2006;98:1381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Xu SZ, et al. TRPC channel activation by extracellular thioredoxin. Nature. 2008;451:69–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron. 2001;29:645–55.

    Article  CAS  PubMed  Google Scholar 

  24. Hou X, Pedi L, Diver MM, Long SB. Crystal structure of the calcium release-activated calcium channel Orai. Science. 2012;338:1308–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thompson JL, Shuttleworth TJ. How many Orai’s does it take to make a CRAC channel? Sci Rep. 2013;3:1961.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Grigoriev I, et al. STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER. Curr Biol. 2008;18:177–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S. STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol. 2007;9:636–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cheong A, et al. Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers. Cardiovasc Res. 2011;89:282–9.

    Article  CAS  PubMed  Google Scholar 

  29. Sweeney M, et al. Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol. 2002;283:L144–55.

    CAS  Google Scholar 

  30. Bergdahl A, et al. Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Am J Physiol Cell Physiol. 2005;288:C872–80.

    Article  CAS  PubMed  Google Scholar 

  31. Kumar B, et al. Upregulated TRPC1 channel in vascular injury in vivo and its role in human neointimal hyperplasia. Circ Res. 2006;98:557–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Naylor J, Beech DJ. Generation of antibodies that are externally acting isoform-specific inhibitors of ion channels. Methods Mol Biol. 2013;998:245–56.

    Article  CAS  PubMed  Google Scholar 

  33. Xu SZ, Beech DJ. TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res. 2001;88:84–7.

    Article  CAS  PubMed  Google Scholar 

  34. Xu SZ, et al. Generation of functional ion-channel tools by E3 targeting. Nat Biotechnol. 2005;23:1289–93.

    Article  CAS  PubMed  Google Scholar 

  35. Xu SZ, Boulay G, Flemming R, Beech DJ. E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. Am J Physiol. 2006;291:H2653–9.

    Article  CAS  Google Scholar 

  36. Zeng W, et al. STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell. 2008;32:439–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li J, et al. Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in vascular smooth muscle cells. Circ Res. 2008;103:e97–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Al-Shawaf E, et al. Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2010;30:1453–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Berliner JA, Watson AD. A role for oxidized phospholipids in atherosclerosis. N Engl J Med. 2005;353:9–11.

    Article  CAS  PubMed  Google Scholar 

  40. Li J, et al. Nanomolar potency and selectivity of a Ca2+ release-activated Ca2+ channel inhibitor against store-operated Ca2+ entry and migration of vascular smooth muscle cells. Br J Pharmacol. 2011;164:382–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cahalan MD. STIMulating store-operated Ca2+ entry. Nat Cell Biol. 2009;11:669–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li J, et al. Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation. Circ Res. 2011;108:1190–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang W, et al. Orai1-mediated ICRAC is essential for neointima formation after vascular injury. Circ Res. 2011;109:534–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Groschner K, et al. TRP proteins form store-operated cation channels in human vascular endothelial cells. FEBS Lett. 1998;437:101–6.

    Article  CAS  PubMed  Google Scholar 

  45. Tiruppathi C, et al. Impairment of store-operated Ca2+ entry in TRPC4(−/−) mice interferes with increase in lung microvascular permeability. Circ Res. 2002;91:70–6.

    Article  CAS  PubMed  Google Scholar 

  46. Cioffi DL, et al. Activation of the endothelial store-operated ISOC Ca2+ channel requires interaction of protein 4.1 with TRPC4. Circ Res. 2005;97:1164–72.

    Article  CAS  PubMed  Google Scholar 

  47. Ma X, et al. Heteromeric TRPV4-C1 channels contribute to store-operated Ca2+ entry in vascular endothelial cells. Cell Calcium. 2011;50:502–9.

    Article  CAS  PubMed  Google Scholar 

  48. Sundivakkam PC, et al. The Ca2+ sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca2+ entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol. 2012;81:510–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hamdollah Zadeh MA, Glass CA, Magnussen A, Hancox JC, Bates DO. VEGF-mediated elevated intracellular calcium and angiogenesis in human microvascular endothelial cells in vitro are inhibited by dominant negative TRPC6. Microcirculation. 2008;15:605–14.

    Article  CAS  PubMed  Google Scholar 

  50. Ge R, et al. Critical role of TRPC6 channels in VEGF-mediated angiogenesis. Cancer Lett. 2009;283:43–51.

    Article  CAS  PubMed  Google Scholar 

  51. Yu PC, Gu SY, Bu JW, Du JL. TRPC1 is essential for in vivo angiogenesis in zebrafish. Circ Res. 2010;106:1221–32.

    Article  CAS  PubMed  Google Scholar 

  52. Antigny F, Girardin N, Frieden M. Transient receptor potential canonical channels are required for in vitro endothelial tube formation. J Biol Chem. 2012;287:5917–27.

    Article  CAS  PubMed  Google Scholar 

  53. Malli R, Naghdi S, Romanin C, Graier WF. Cytosolic Ca2+ prevents the subplasmalemmal clustering of STIM1: an intrinsic mechanism to avoid Ca2+ overload. J Cell Sci. 2008;121:3133–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS. Local Ca2+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca2+ signals required for specific cell functions. PLoS Biol. 2011;9:e1001025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rosenbaum MA, Chaudhuri P, Graham LM. Hypercholesterolemia inhibits re-endothelialization of arterial injuries by TRPC channel activation. J Vasc Surg. 2014;62(4):1040–7. S0741-5214(14)00834-9.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Our work in this area has been supported by research grants from the Wellcome Trust, Medical Research Council and British Heart Foundation. H.L.A. is supported by a Studentship from the British Heart Foundation.

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Authors and Affiliations

  1. School of Medicine, University of Leeds, LIGHT Building, Clarendon Way, Leeds, LS2 9JT, UK

    David J. Beech, Jing Li, Lynn McKeown & Hollie L. Appleby

Authors
  1. David J. Beech
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  2. Jing Li
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  3. Lynn McKeown
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  4. Hollie L. Appleby
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Corresponding author

Correspondence to David J. Beech .

Editor information

Editors and Affiliations

  1. University of Illinois at Chicago, Chicago, Illinois, USA

    Irena Levitan, PhD

  2. The University of Tennessee, Memphis, Tennessee, USA

    Alex M. Dopico, MD, PhD

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© 2016 Springer International Publishing Switzerland

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Beech, D.J., Li, J., McKeown, L., Appleby, H.L. (2016). TRPC and Orai Channels in Store-Operated Calcium Entry and Vascular Remodelling. In: Levitan, PhD, I., Dopico, MD, PhD, A. (eds) Vascular Ion Channels in Physiology and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-29635-7_13

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