Abstract
The endothelium is a highly metabolically active organ that plays a pivotal role in many physiological processes. Endothelial cells express a diversity of calcium-permeable ion channels that can be activated in response to a variety of stimuli including Ca2+ store depletion, oxidative stress, growth factors, and endotoxins. Emerging evidences have implicated the critical requirement of Ca2+ signaling in numerous vascular functions including vasomotor tone, barrier function, leukocyte homing and adhesion, inflammation, and hemostasis. The goal of this chapter is to present a comprehensive review of the expression and regulatory mechanisms of Ca2+ channels in endothelial cells, and discuss their contribution to vascular endothelial cell physiology and pathophysiology processes.
References
Augustin HG, Kozian DH, Johnson RC. Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. Bioessays. 1994;16:901–6.
Fishman AP. Endothelium: a distributed organ of diverse capabilities. Ann N Y Acad Sci. 1982;401:1–8.
Muller MM, Griesmacher A. Markers of endothelial dysfunction. Clin Chem Lab Med. 2000;38:77–85.
Jaffe EA. Cell biology of endothelial cells. Hum Pathol. 1987;18:234–9.
Cook-Mills JM, Deem TL. Active participation of endothelial cells in inflammation. J Leukoc Biol. 2005;77:487–95.
Santiago-Delpin EA. The endothelium and early immune activation: new perspective and interactions. Transplant Proc. 2004;36:1709–13.
Biedermann BC. Vascular endothelium: checkpoint for inflammation and immunity. News Physiol Sci. 2001;16:84–8.
Lum H, Malik AB. Regulation of vascular endothelial barrier function. Am J Physiol. 1994;267:L223–41.
Cines DB, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527–61.
Yao X, Garland CJ. Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res. 2005;97:853–63.
Tiruppathi C, Ahmmed GU, Vogel SM, Malik AB. Ca2+ signaling, TRP channels, and endothelial permeability. Microcirculation. 2006;13:693–708.
Ahmmed GU, Malik AB. Functional role of TRPC channels in the regulation of endothelial permeability. Pflugers Arch. 2005;451:131–42.
Putney Jr JW. A model for receptor-regulated calcium entry. Cell Calcium. 1986;7:1–12.
Parekh AB, Putney Jr JW. Store-operated calcium channels. Physiol Rev. 2005;85:757–810.
Amiri H, Schultz G, Schaefer M. FRET-based analysis of TRPC subunit stoichiometry. Cell Calcium. 2003;33:463–70.
Montell C. The TRP superfamily of cation channels. Sci STKE. 2005;2005:re3.
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.
Du J, et al. TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. FASEB J. 2014;28:4677–85.
Ma X, et al. Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. Cell Calcium. 2011;50:502–9.
Garcia RL, Schilling WP. Differential expression of mammalian TRP homologues across tissues and cell lines. Biochem Biophys Res Commun. 1997;239:279–83.
Paria BC, et al. Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability. Am J Physiol Lung Cell Mol Physiol. 2004;287:L1303–13.
Kohler R, et al. Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells. Cardiovasc Res. 2001;51:160–8.
Yip H, et al. Expression of TRPC homologs in endothelial cells and smooth muscle layers of human arteries. Histochem Cell Biol. 2004;122:553–61.
Liou J, et al. STIM is a Ca2+ sensor essential for Ca2 + -store-depletion-triggered Ca2+ influx. Curr Biol. 2005;15:1235–41.
Roos J, et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol. 2005;169:435–45.
Zhang SL, et al. STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature. 2005;437:902–5.
Yuan JP, et al. SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol. 2009;11:337–43.
Park CY, et al. STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell. 2009;136:876–90.
Kawasaki T, Lange I, Feske S. A minimal regulatory domain in the C terminus of STIM1 binds to and activates ORAI1 CRAC channels. Biochem Biophys Res Commun. 2009;385:49–54.
Liou J, Fivaz M, Inoue T, Meyer T. Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion. Proc Natl Acad Sci U S A. 2007;104:9301–6.
Zeng W, et al. STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell. 2008;32:439–48.
Hogan PG, Lewis RS, Rao A. Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol. 2010;28:491–533.
Stathopulos PB, Ikura M. Structural aspects of calcium-release activated calcium channel function. Channels (Austin). 2013;7:344–53.
Parekh AB, Penner R. Store depletion and calcium influx. Physiol Rev. 1997;77:901–30.
Feske S, et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006;441:179–85.
Vig M, et al. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006;312:1220–3.
Liao Y, et al. Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci U S A. 2007;104:4682–7.
Ong HL, et al. Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J Biol Chem. 2007;282:9105–16.
Prakriya M, et al. Orai1 is an essential pore subunit of the CRAC channel. Nature. 2006;443:230–3.
Faehling M, et al. Essential role of calcium in vascular endothelial growth factor A-induced signaling: mechanism of the antiangiogenic effect of carboxyamidotriazole. FASEB J. 2002;16:1805–7.
Fasolato C, Nilius B. Store depletion triggers the calcium release-activated calcium current (ICRAC) in macrovascular endothelial cells: a comparison with Jurkat and embryonic kidney cell lines. Pflugers Arch. 1998;436:69–74.
Sundivakkam PC, et al. The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol. 2012;81:510–26.
Li J, et al. Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation. Circ Res. 2011;108:1190–8.
Abdullaev IF, et al. Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res. 2008;103:1289–99.
Sayner SL, Balczon R, Frank DW, Cooper DM, Stevens T. Filamin A is a phosphorylation target of membrane but not cytosolic adenylyl cyclase activity. Am J Physiol Lung Cell Mol Physiol. 2011;301:L117–24.
Dietrich A, Gudermann T. Another TRP to endothelial dysfunction: TRPM2 and endothelial permeability. Circ Res. 2008;102:275–7.
Groschner K, Rosker C, Lukas M. Role of TRP channels in oxidative stress. Novartis Found Symp. 2004;258:222–30. discussion 231–225, 263–226.
Hecquet CM, Ahmmed GU, Vogel SM, Malik AB. Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res. 2008;102:347–55.
Hecquet CM, Malik AB. Role of H(2)O(2)-activated TRPM2 calcium channel in oxidant-induced endothelial injury. Thromb Haemost. 2009;101:619–25.
Kwan HY, Huang Y, Yao X. TRP channels in endothelial function and dysfunction. Biochim Biophys Acta. 2007;1772:907–14.
Inoue K, Xiong ZG. Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway. Cardiovasc Res. 2009;83:547–57.
Sun H, et al. Role of TRPM7 channels in hyperglycemia-mediated injury of vascular endothelial cells. PLoS One. 2013;8:e79540.
Sarmiento D, et al. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel. Microvasc Res. 2014;98:187–96.
Kaupp UB, Seifert R. Cyclic nucleotide-gated ion channels. Physiol Rev. 2002;82:769–824.
Cheng KT, Chan FL, Huang Y, Chan WY, Yao X. Expression of olfactory-type cyclic nucleotide-gated channel (CNGA2) in vascular tissues. Histochem Cell Biol. 2003;120:475–81.
Yao X, Leung PS, Kwan HY, Wong TP, Fong MW. Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells. Cardiovasc Res. 1999;41:282–90.
Zhang J, Xia SL, Block ER, Patel JM. NO upregulation of a cyclic nucleotide-gated channel contributes to calcium elevation in endothelial cells. Am J Physiol Cell Physiol. 2002;283:C1080–9.
Lum H, Del Vecchio PJ, Schneider AS, Goligorsky MS, Malik AB. Calcium dependence of the thrombin-induced increase in endothelial albumin permeability. J Appl Physiol (1985). 1989;66:1471–6.
Ellis CA, et al. Thrombin induces proteinase-activated receptor-1 gene expression in endothelial cells via activation of Gi-linked Ras/mitogen-activated protein kinase pathway. J Biol Chem. 1999;274:13718–27.
Vogel SM, et al. Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout mice. Physiol Genomics. 2000;4:137–45.
Singh I, et al. Galphaq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant endothelial cell shape change in response to thrombin. J Biol Chem. 2007;282:7833–43.
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.
Jho D, et al. Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx. Circ Res. 2005;96:1282–90.
Mehta D, et al. RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J Biol Chem. 2003;278:33492–500.
Paria BC, et al. Ca2+ influx induced by protease-activated receptor-1 activates a feed-forward mechanism of TRPC1 expression via nuclear factor-kappaB activation in endothelial cells. J Biol Chem. 2006;281:20715–27.
Moore TM, et al. Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1. Am J Physiol. 1998;275:L574–82.
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.
Odell AF, Van Helden DF, Scott JL. The spectrin cytoskeleton influences the surface expression and activation of human transient receptor potential channel 4 channels. J Biol Chem. 2008;283:4395–407.
Hofmann T, et al. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999;397:259–63.
Kini V, Chavez A, Mehta D. A new role for PTEN in regulating transient receptor potential canonical channel 6-mediated Ca2+ entry, endothelial permeability, and angiogenesis. J Biol Chem. 2010;285:33082–91.
Shinde AV, et al. STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry. Sci Signal. 2012;6:ra18.
Salido GM, Sage SO, Rosado JA. TRPC channels and store-operated Ca(2+) entry. Biochim Biophys Acta. 2009;1793:223–30.
Zhang W, et al. A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. J Biol Chem. 2003;278:16222–9.
Glass CA, Pocock TM, Curry FE, Bates DO. Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo. J Physiol. 2005;564:817–27.
Hong JH, et al. Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells. Traffic. 2011;12:232–45.
Petersen OH, Tepikin AV. Polarized calcium signaling in exocrine gland cells. Annu Rev Physiol. 2008;70:273–99.
Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS. Local Ca(2) + entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca(2) + signals required for specific cell functions. PLoS Biol. 2011;9:e1001025.
Fleming I, Busse R. NO: the primary EDRF. J Mol Cell Cardiol. 1999;31:5–14.
Feletou M, Vanhoutte PM. The alternative: EDHF. J Mol Cell Cardiol. 1999;31:15–22.
Drexler H, Hornig B. Endothelial dysfunction in human disease. J Mol Cell Cardiol. 1999;31:51–60.
Boulanger CM, Vanhoutte PM. G proteins and endothelium-dependent relaxations. J Vasc Res. 1997;34:175–85.
Kamouchi M, et al. Properties of heterologously expressed hTRP3 channels in bovine pulmonary artery endothelial cells. J Physiol. 1999;518(Pt 2):345–58.
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.
Randall MD, Kendall DA. Anandamide and endothelium-derived hyperpolarizing factor act via a common vasorelaxant mechanism in rat mesentery. Eur J Pharmacol. 1998;346:51–3.
Watanabe H, et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature. 2003;424:434–8.
Sonkusare SK, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336:597–601.
Cheng KT, et al. CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:913–8.
Shen B, et al. Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels. J Mol Cell Cardiol. 2008;45:437–45.
Kwan HY, et al. CNGA2 contributes to ATP-induced noncapacitative Ca2+ influx in vascular endothelial cells. J Vasc Res. 2009;47:148–56.
Nilius B, Droogmans G. Ion channels and their functional role in vascular endothelium. Physiol Rev. 2001;81:1415–59.
Brock TA, Dvorak HF, Senger DR. Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol. 1991;138:213–21.
Faehling M, Koch ED, Raithel J, Trischler G, Waltenberger J. Vascular endothelial growth factor-A activates Ca2+ -activated K+ channels in human endothelial cells in culture. Int J Biochem Cell Biol. 2001;33:337–46.
Cheng HW, James AF, Foster RR, Hancox JC, Bates DO. VEGF activates receptor-operated cation channels in human microvascular endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26:1768–76.
Pocock TM, Foster RR, Bates DO. Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo. Am J Physiol Heart Circ Physiol. 2004;286:H1015–26.
Ge R, et al. Critical role of TRPC6 channels in VEGF-mediated angiogenesis. Cancer Lett. 2009;283:43–51.
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.
Fantozzi I, et al. Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1233–45.
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.
Chen YF, et al. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci U S A. 2011;108:15225–30.
Lodola F, et al. Store-operated Ca2+ entry is remodelled and controls in vitro angiogenesis in endothelial progenitor cells isolated from tumoral patients. PLoS One. 2012;7:e42541.
Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012;2:a006429.
Touyz RM. Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension. Am J Physiol Heart Circ Physiol. 2008;294:H1103–18.
Owsianik G, Talavera K, Voets T, Nilius B. Permeation and selectivity of TRP channels. Annu Rev Physiol. 2006;68:685–717.
Wolf FI, Cittadini A. Magnesium in cell proliferation and differentiation. Front Biosci. 1999;4:D607–17.
Sgambato A, Wolf FI, Faraglia B, Cittadini A. Magnesium depletion causes growth inhibition, reduced expression of cyclin D1, and increased expression of P27Kip1 in normal but not in transformed mammary epithelial cells. J Cell Physiol. 1999;180:245–54.
Fiorio Pla A, et al. Arachidonic acid-induced Ca2+ entry is involved in early steps of tumor angiogenesis. Mol Cancer Res. 2008;6:535–45.
Fiorio Pla A, et al. TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene. 2012;31:200–12.
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–95.
Hoth M, Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature. 1992;355:353–6.
Nilius B, Owsianik G. Transient receptor potential channelopathies. Pflugers Arch. 2010;460:437–50.
Danese S, Dejana E, Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol. 2007;178:6017–22.
Tauseef M, et al. TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation. J Exp Med. 2012;209:1953–68.
Gandhirajan RK, et al. Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J Clin Invest. 2013;123:887–902.
DebRoy A, et al. Cooperative signaling via transcription factors NF-kappaB and AP1/c-Fos mediates endothelial cell STIM1 expression and hyperpermeability in response to endotoxin. J Biol Chem. 2014;289:24188–201.
Lombardi L, et al. Chemokine receptor CXCR4: role in gastrointestinal cancer. Crit Rev Oncol Hematol. 2013;88:696–705.
Zhou MH, et al. Stromal interaction molecule 1 (STIM1) and Orai1 mediate histamine-evoked calcium entry and nuclear factor of activated T-cells (NFAT) signaling in human umbilical vein endothelial cells. J Biol Chem. 2014;289:29446–56.
Acknowledgement
We thank Kit Man Tsang for manuscript editing and Katrian Cheng for support. This work was supported by NIH grant HL077806 to A.B.M.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Cheng, K.T., Rosenhouse-Dantsker, A., Malik, A.B. (2016). Contribution and Regulation of Calcium Channels in Endothelial Cells. 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_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-29635-7_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29633-3
Online ISBN: 978-3-319-29635-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)