Skip to main content

Endothelial Cell Ion Channel Expression and Function in Arterioles and Resistance Arteries

  • Chapter
  • First Online:
Vascular Ion Channels in Physiology and Disease

Abstract

Ion channels importantly contribute to the function of endothelial cells. They serve as the major source of intracellular Ca2+, which, in turn, controls the production of endothelium-derived vasodilators, the permeability of the endothelium, gene expression, and other properties of endothelial cells. In addition, the activity of ion channels determines the membrane potential of endothelial cells that serves as an important signal for cell-cell communication between endothelial cells and between endothelial cells and overlying smooth muscle cells, and may feed-back to regulate the activity of the ion channels themselves. This review provides an overview of the expression and function of endothelial ion channels that contribute to Ca2+ and membrane potential signaling that is involved in the regulation and modulation of vasomotor tone of resistance arteries and arterioles. Channels discussed include inositol 1,4,5 trisphosphate receptors that mediate agonist-induced Ca2+ release from endoplasmic reticulum stores; members of the transient receptor potential family and other channels that mediate agonist-induced Ca2+ influx through the plasma membrane; Ca2+-activated K+ channels that mediate agonist-induced membrane hyperpolarization; and inward rectifier K+ channels that serve as sensors for changes in extracellular K+ and amplifiers of hyperpolarization induced by the activity of other ion channels. It is emphasized that all of these channels exist as members of macromolecular signaling complexes providing a rich environment for regulation of their activity and the function of endothelial cells in resistance arteries and arterioles.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  1. Abdullaev IF, Bisaillon JM, Potier M, Gonzalez JC, Motiani RK, Trebak M. Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res. 2008;103:1289–99.

    CAS  Google Scholar 

  2. Absi M, Burnham MP, Weston AH, Harno E, Rogers M, Edwards G. Effects of methyl beta-cyclodextrin on EDHF responses in pig and rat arteries; association between SK(Ca) channels and caveolin-rich domains. Br J Pharmacol. 2007;151:332–40.

    CAS  Google Scholar 

  3. Adams DJ, Hill MA. Potassium channels and membrane potential in the modulation of intracellular calcium in vascular endothelial cells. J Cardiovasc Electrophysiol. 2004;15:598–610.

    Google Scholar 

  4. Adebiyi A, Zhao G, Narayanan D, Thomas-Gatewood CM, Bannister JP, Jaggar JH. Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility. Circ Res. 2010;106:1603–12.

    CAS  Google Scholar 

  5. Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB. Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. J Biol Chem. 2004;279:20941–9.

    CAS  Google Scholar 

  6. Alagem N, Dvir M, Reuveny E. Mechanism of Ba2+ block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues. J Physiol Lond. 2001;534:381–93.

    CAS  Google Scholar 

  7. Antoniotti S, Lovisolo D, Fiorio Pla A, Munaron L. Expression and functional role of bTRPC1 channels in native endothelial cells. FEBS Lett. 2002;510:189–95.

    CAS  Google Scholar 

  8. Bagher P, Beleznai T, Kansui Y, Mitchell R, Garland CJ, Dora KA. Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone. Proc Natl Acad Sci U S A. 2012;109:18174–9.

    CAS  Google Scholar 

  9. Baraldi PG, Preti D, Materazzi S, Geppetti P. Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem. 2010;53:5085–107.

    CAS  Google Scholar 

  10. Beech DJ, Xu SZ, McHugh D, Flemming R. TRPC1 store-operated cationic channel subunit. Cell Calcium. 2003;33:433–40.

    CAS  Google Scholar 

  11. Bergdahl A, Gomez MF, Wihlborg A-K, Erlinge D, Eyjolfson A, Xu S-Z, Beech DJ, Dreja K, Hellstrand P. Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Am J Physiol Cell Physiol. 2005;288:C872–80.

    CAS  Google Scholar 

  12. Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA. Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol. 2008;295:C779–90.

    CAS  Google Scholar 

  13. Berridge M. Inositol trisphosphate and calcium signalling. Nature. 1993;361:315–25.

    CAS  Google Scholar 

  14. Boulay G, Zhu X, Peyton M, Jiang M, Hurst R, Stefani E, Birnbaumer L. Cloning and expression of a novel mammalian homolog of Drosophila Transient Receptor Potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J Biol Chem. 1997;272:29672–80.

    CAS  Google Scholar 

  15. Brahler S, Kaistha A, Schmidt VJ, Wolfle SE, Busch C, Kaistha BP, Kacik M, Hasenau AL, Grgic I, Si H, Bond CT, Adelman JP, Wulff H, de Wit C, Hoyer J, Kohler R. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation. 2009;119:2323–32.

    Google Scholar 

  16. Braunstein TH, Inoue R, Cribbs L, Oike M, Ito Y, Holstein-Rathlou NH, Jensen LJ. The role of L- and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles. J Vasc Res. 2009;46:138–51.

    CAS  Google Scholar 

  17. Brough GH, Wu S, Cioffi D, Moore TM, Li M, Dean N, Stevens T. Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway. FASEB J. 2001;15:1727–38.

    CAS  Google Scholar 

  18. Busse R, Fichtner H, Luckhoff A, Kohlhardt M. Hyperpolarization and increased free calcium in acetylcholine-stimulated endothelial cells. Am J Physiol. 1988;255:H965–9.

    CAS  Google Scholar 

  19. Bychkov R, Burnham MP, Richards GR, Edwards G, Weston AH, Feletou M, Vanhoutte PM. Characterization of a charybdotoxin-sensitive intermediate conductance Ca2+-activated K+ channel in porcine coronary endothelium: relevance to EDHF. Br J Pharmacol. 2002;137:1346–54.

    CAS  Google Scholar 

  20. Chatterjee S, Al-Mehdi AB, Levitan I, Stevens T, Fisher AB. Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells. Am J Physiol Cell Physiol. 2003;285:C959–67.

    CAS  Google Scholar 

  21. Chen W, Oberwinkler H, Werner F, Gassner B, Nakagawa H, Feil R, Hofmann F, Schlossmann J, Dietrich A, Gudermann T, Nishida M, Del Galdo S, Wieland T, Kuhn M. Atrial natriuretic peptide-mediated inhibition of microcirculatory endothelial Ca2+ and permeability response to histamine involves cGMP-dependent protein kinase I and TRPC6 channels. Arterioscler Thromb Vasc Biol. 2013;33:2121–9.

    CAS  Google Scholar 

  22. Cipolla MJ, Smith J, Kohlmeyer MM, Godfrey JA. SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion. Stroke. 2009;40:1451–7.

    Google Scholar 

  23. Cohen KD, Jackson WF. Membrane hyperpolarization is not required for sustained muscarinic agonist-induced increases in intracellular Ca2+ in arteriolar endothelial cells. Microcirculation. 2005;12:169–82.

    CAS  Google Scholar 

  24. Colden-Stanfield M, Schilling WP, Possani LD, Kunze DL. Bradykinin-induced potassium current in cultured bovine aortic endothelial cells. J Membr Biol. 1990;116:227–38.

    CAS  Google Scholar 

  25. Colden-Stanfield M, Schilling WP, Ritchie AK, Eskin SG, Navarro LT, Kunze DL. Bradykinin-induced increases in cytosolic calcium and ionic currents in cultured bovine aortic endothelial cells. Circ Res. 1987;61:632–40.

    CAS  Google Scholar 

  26. Corriu C, Feletou M, Canet E, Vanhoutte PM. Endothelium-derived factors and hyperpolarization of the carotid artery of the guinea-pig. Br J Pharmacol. 1996;119:959–64.

    CAS  Google Scholar 

  27. Crane GJ, Gallagher N, Dora KA, Garland CJ. Small- and intermediate-conductance calcium-activated K+ channels provide different facets of endothelium-dependent hyperpolarization in rat mesenteric artery. J Physiol. 2003;553:183–9.

    CAS  Google Scholar 

  28. Crane GJ, Walker SD, Dora KA, Garland CJ. Evidence for a differential cellular distribution of inward rectifier K channels in the rat isolated mesenteric artery. J Vasc Res. 2003;40:159–68.

    CAS  Google Scholar 

  29. de Wit C, Griffith TM. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch. 2010;459:897–914.

    Google Scholar 

  30. Dietrich A, Fahlbusch M, Gudermann T. Classical Transient Receptor Potential 1 (TRPC1): channel or channel regulator? Cells. 2014;3:939–62.

    CAS  Google Scholar 

  31. Dietrich A, Kalwa H, Storch U, Mederos Y, Schnitzler M, Salanova B, Pinkenburg O, Dubrovska G, Essin K, Gollasch M, Birnbaumer L, Gudermann T. Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1. Pflugers Arch. 2007;455:465–77.

    CAS  Google Scholar 

  32. Dora KA, Doyle MP, Duling BR. Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles. Proc Natl Acad Sci U S A. 1997;94:6529–34.

    CAS  Google Scholar 

  33. Dora KA, Gallagher NT, McNeish A, Garland CJ. Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circ Res. 2008;102:1247–55.

    CAS  Google Scholar 

  34. Dora KA, Garland CJ. Linking hyperpolarization to endothelial cell calcium events in arterioles. Microcirculation. 2013;20:248–56.

    CAS  Google Scholar 

  35. Du J, Ma X, Shen B, Huang Y, Birnbaumer L, Yao X. TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. FASEB J. 2014;28:4677–85.

    CAS  Google Scholar 

  36. Duza T, Sarelius IH. Localized transient increases in endothelial cell Ca2+ in arterioles in situ: implications for the coordination of vascular function. Am J Physiol Heart Circ Physiol. 2004;286:H2322–31.

    CAS  Google Scholar 

  37. Earley S, Gonzales AL, Crnich R. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-activated K+ channels. Circ Res. 2009;104:987–94.

    CAS  Google Scholar 

  38. Earley S, Gonzales AL, Garcia ZI. A dietary agonist of transient receptor potential cation channel V3 elicits endothelium-dependent vasodilation. Mol Pharmacol. 2010;77:612–20.

    CAS  Google Scholar 

  39. Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden JE. TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol Heart Circ Physiol. 2009;297:H1096–102.

    CAS  Google Scholar 

  40. Edwards G, Feletou M, Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch. 2010;459:863–79.

    CAS  Google Scholar 

  41. Eichler I, Wibawa J, Grgic I, Knorr A, Brakemeier S, Pries AR, Hoyer J, Kohler R. Selective blockade of endothelial Ca2+-activated small- and intermediate-conductance K+-channels suppresses EDHF-mediated vasodilation. Br J Pharmacol. 2003;138:594–601.

    CAS  Google Scholar 

  42. Estacion M, Li S, Sinkins WG, Gosling M, Bahra P, Poll C, Westwick J, Schilling WP. Activation of human TRPC6 channels by receptor stimulation. J Biol Chem. 2004;279:22047–56.

    CAS  Google Scholar 

  43. Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, Hayward NJ, McNamara CR, Xue F, Moran MM, Strassmaier T, Uykal E, Owsianik G, Vennekens R, De Ridder D, Nilius B, Fanger CM, Voets T. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc Natl Acad Sci U S A. 2010;107:19084–9.

    CAS  Google Scholar 

  44. Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J. Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem. 1999;274:5746–54.

    CAS  Google Scholar 

  45. Figueroa XF, Chen CC, Campbell KP, Damon DN, Day KH, Ramos S, Duling BR. Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone? Am J Physiol Heart Circ Physiol. 2007;293:H1371–83.

    CAS  Google Scholar 

  46. Fill M, Copello JA. Ryanodine receptor calcium release channels. Physiol Rev. 2002;82:893–922.

    CAS  Google Scholar 

  47. Foskett J, White C, Cheung K, Mak D. Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev. 2007;87:593–658.

    CAS  Google Scholar 

  48. Freichel M, Suh SH, Pfeifer A, Schweig U, Trost C, Weissgerber P, Biel M, Philipp S, Freise D, Droogmans G, Hofmann F, Flockerzi V, Nilius B. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice. Nat Cell Biol. 2001;3:121–7.

    CAS  Google Scholar 

  49. Gafni J, Munsch JA, Lam TH, Catlin MC, Costa LG, Molinski TF, Pessah IN. Xestospongins: potent membrane permeable blockers of the inositol 1,4,5-trisphosphate receptor. Neuron. 1997;19:723.

    CAS  Google Scholar 

  50. Gauthier KM, Liu C, Popovic A, Albarwani S, Rusch NJ. Freshly isolated bovine coronary endothelial cells do not express the BK(Ca) channel gene. J Physiol. 2002;545:829–36.

    CAS  Google Scholar 

  51. Gees M, Colsoul B, Nilius B. The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol. 2010;2:a003962.

    CAS  Google Scholar 

  52. Goddard LM, Iruela-Arispe ML. Cellular and molecular regulation of vascular permeability. Thromb Haemost. 2013;109:407–15.

    CAS  Google Scholar 

  53. Gordon JL, Martin W. Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells. Br J Pharmacol. 1983;79:531–41.

    CAS  Google Scholar 

  54. Graier WF, Paltauf-Doburzynska J, Hill BJ, Fleischhacker E, Hoebel BG, Kostner GM, Sturek M. Submaximal stimulation of porcine endothelial cells causes focal Ca2+ elevation beneath the cell membrane. J Physiol. 1998;506(Pt 1):109–25.

    CAS  Google Scholar 

  55. Graier WF, Simecek S, Bowles DK, Sturek M. Heterogeneity of caffeine- and bradykinin-sensitive Ca2+ stores in vascular endothelial cells. Biochem J. 1994;300:637–41.

    CAS  Google Scholar 

  56. Grayson TH, Haddock RE, Murray TP, Wojcikiewicz RJH, Hill CE. Inositol 1,4,5-trisphosphate receptor subtypes are differentially distributed between smooth muscle and endothelial layers of rat arteries. Cell Calcium. 2004;36:447.

    CAS  Google Scholar 

  57. Grgic I, Kaistha BP, Hoyer J, Kohler R. Endothelial Ca+-activated K+ channels in normal and impaired EDHF-dilator responses—relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol. 2009;157:509–26.

    CAS  Google Scholar 

  58. Halaszovich CR, Zitt C, Jungling E, Luckhoff A. Inhibition of TRP3 channels by lanthanides. Block from the cytosolic side of the plasma membrane. J Biol Chem. 2000;275:37423–8.

    CAS  Google Scholar 

  59. Hallam TJ, Pearson JD. Exogenous ATP raises cytoplasmic free calcium in fura-2 loaded piglet aortic endothelial cells. FEBS Lett. 1986;207:95–9.

    CAS  Google Scholar 

  60. 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.

    CAS  Google Scholar 

  61. Hamilton S. Ryanodine receptors. Cell Calcium. 2005;38:253–60.

    CAS  Google Scholar 

  62. Hamilton S, Serysheva I. Ryanodine receptor structure: progress and challenges. J Biol Chem. 2009;284:4047–51.

    CAS  Google Scholar 

  63. Hannah RM, Dunn KM, Bonev AD, Nelson MT. Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow. J Cereb Blood Flow Metab. 2011;31:1175–86.

    CAS  Google Scholar 

  64. Harteneck C, Gollasch M. Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels. Curr Pharm Biotechnol. 2011;12:35–41.

    CAS  Google Scholar 

  65. He P, Curry FE. Depolarization modulates endothelial cell calcium influx and microvessel permeability. Am J Physiol Heart Circ Physiol. 1991;261:H1246–54.

    CAS  Google Scholar 

  66. He P, Curry FE. Endothelial cell hyperpolarization increases [Ca2+]i and venular microvessel permeability. J Appl Physiol. 1994;76:2288–97.

    CAS  Google Scholar 

  67. Heady TN, Gomora JC, Macdonald TL, Perez-Reyes E. Molecular pharmacology of T-type Ca < sup > 2 + </sup > channels. Jpn J Pharmacol. 2001;85:339–50.

    CAS  Google Scholar 

  68. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010;90:291–366.

    CAS  Google Scholar 

  69. Himmel HM, Whorton AR, Strauss HC. Intracellular calcium, currents, and stimulus-response coupling in endothelial cells. Hypertension. 1993;21:112–27.

    CAS  Google Scholar 

  70. Hoffmann EK, Lambert IH, Pedersen SF. Physiology of cell volume regulation in vertebrates. Physiol Rev. 2009;89:193–277.

    CAS  Google Scholar 

  71. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999;397:259–63.

    CAS  Google Scholar 

  72. Hondeghem LM, Ayad MJ, Robertson RM. Verapamil, diltiazem and nifedipine block the depolarization-induced potentiation of norepinephrine contractions in rabbit aorta and porcine coronary arteries. J Pharmacol Exp Ther. 1986;239:808–13.

    CAS  Google Scholar 

  73. Hoshi T, Pantazis A, Olcese R. Transduction of voltage and Ca2+ signals by Slo1 BK channels. Physiology (Bethesda). 2013;28:172–89.

    CAS  Google Scholar 

  74. Hoyer J, Popp R, Meyer J, Galla HJ, Gogelein H. Angiotensin II, vasopressin and GTP[gamma-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells. J Membr Biol. 1991;123:55–62.

    CAS  Google Scholar 

  75. Huang JH, He GW, Xue HM, Yao XQ, Liu XC, Underwood MJ, Yang Q. TRPC3 channel contributes to nitric oxide release: significance during normoxia and hypoxia-reoxygenation. Cardiovasc Res. 2011;91:472–82.

    CAS  Google Scholar 

  76. Hughes JM, Riddle MA, Paffett ML, Gonzalez Bosc LV, Walker BR. Novel role of endothelial BKCa channels in altered vasoreactivity following hypoxia. Am J Physiol Heart Circ Physiol. 2010;299:H1439–50.

    CAS  Google Scholar 

  77. Isakson BE. Localized expression of an Ins(1,4,5)P3 receptor at the myoendothelial junction selectively regulates heterocellular Ca2+ communication. J Cell Sci. 2008;121:3664–73.

    CAS  Google Scholar 

  78. Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, Maylie J. A human intermediate conductance calcium-activated potassium channel. Proc Natl Acad Sci U S A. 1997;94:11651–6.

    CAS  Google Scholar 

  79. Jackson WF. The endothelium-derived relaxing factor. J Reconstr Microsurg. 1989;5(3):263–71.

    CAS  Google Scholar 

  80. Jackson WF. Ion channels and vascular tone. Hypertension. 2000;35(1 Pt 2):173–8.

    CAS  Google Scholar 

  81. Jackson WF. Potassium channels in the peripheral microcirculation. Microcirculation. 2005;12:113–27.

    CAS  Google Scholar 

  82. Jantzi MC, Brett SE, Jackson WF, Corteling RL, Vigmond EJ, Welsh DG. Inward rectifying potassium channels facilitate cell-to-cell communication in hamster retractor muscle feed arteries. Am J Physiol Heart Circ Physiol. 2006;291:H1319–28.

    CAS  Google Scholar 

  83. Kansui Y, Garland CJ, Dora KA. Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries. Cell Calcium. 2008;44:135–46.

    CAS  Google Scholar 

  84. Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y. Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc Natl Acad Sci U S A. 2009;106:5400–5.

    CAS  Google Scholar 

  85. Knot HJ, Zimmermann PA, Nelson MT. Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. J Physiol. 1996;492(Pt 2):419–30.

    CAS  Google Scholar 

  86. Kochukov MY, Balasubramanian A, Abramowitz J, Birnbaumer L, Marrelli SP. Activation of endothelial transient receptor potential C3 channel is required for small conductance calcium-activated potassium channel activation and sustained endothelial hyperpolarization and vasodilation of cerebral artery. J Am Heart Assoc. 2014;3.

    Google Scholar 

  87. Kochukov MY, Balasubramanian A, Noel RC, Marrelli SP. Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta. J Vasc Res. 2013;50:11–20.

    CAS  Google Scholar 

  88. Kohler R, Brakemeier S, Kuhn M, Behrens C, Real R, Degenhardt C, Orzechowski HD, Pries AR, Paul M, Hoyer J. Impaired hyperpolarization in regenerated endothelium after balloon catheter injury. Circ Res. 2001;89:174–9.

    CAS  Google Scholar 

  89. Kohler R, Brakemeier S, Kuhn M, Degenhardt C, Buhr H, Pries A, Hoyer J. 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.

    CAS  Google Scholar 

  90. Komarova Y, Malik AB. Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol. 2010;72:463–93.

    CAS  Google Scholar 

  91. Kuo IY, Ellis A, Seymour VA, Sandow SL, Hill CE. Dihydropyridine-insensitive calcium currents contribute to function of small cerebral arteries. J Cereb Blood Flow Metab. 2010;30:1226–39.

    CAS  Google Scholar 

  92. Kwiatek AM, Minshall RD, Cool DR, Skidgel RA, Malik AB, Tiruppathi C. Caveolin-1 regulates store-operated Ca2+ influx by binding of its scaffolding domain to transient receptor potential channel-1 in endothelial cells. Mol Pharmacol. 2006;70:1174–83.

    CAS  Google Scholar 

  93. Ledoux J, Taylor MS, Bonev AD, Hannah RM, Solodushko V, Shui B, Tallini Y, Kotlikoff MI, Nelson MT. Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc Natl Acad Sci U S A. 2008;105:9627–32.

    CAS  Google Scholar 

  94. Lee JH, Gomora JC, Cribbs LL, Perez-Reyes E. Nickel block of three cloned T-type calcium channels: low concentrations selectively block alpha1H. Biophys J. 1999;77:3034–42.

    CAS  Google Scholar 

  95. Lesh RE, Marks AR, Somlyo AV, Fleischer S, Somlyo AP. Anti-ryanodine receptor antibody binding sites in vascular and endocardial endothelium. Circ Res. 1993;72:481–8.

    CAS  Google Scholar 

  96. Leuner K, Heiser JH, Derksen S, Mladenov MI, Fehske CJ, Schubert R, Gollasch M, Schneider G, Harteneck C, Chatterjee SS, Muller WE. Simple 2,4-diacylphloroglucinols as classic transient receptor potential-6 activators--identification of a novel pharmacophore. Mol Pharmacol. 2010;77:368–77.

    CAS  Google Scholar 

  97. Liao P, Yu D, Li G, Yong TF, Soon JL, Chua YL, Soong TW. A smooth muscle Cav1.2 calcium channel splice variant underlies hyperpolarized window current and enhanced state-dependent inhibition by nifedipine. J Biol Chem. 2007;282:35133–42.

    CAS  Google Scholar 

  98. Liu CL, Huang Y, Ngai CY, Leung YK, Yao XQ. TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries. Acta Pharmacol Sin. 2006;27:981–90.

    CAS  Google Scholar 

  99. Liu GX, Derst C, Schlichthorl G, Heinen S, Seebohm G, Bruggemann A, Kummer W, Veh RW, Daut J, Preisig-Muller R. Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes. J Physiol. 2001;532:115–26.

    CAS  Google Scholar 

  100. Loga F, Domes K, Freichel M, Flockerzi V, Dietrich A, Birnbaumer L, Hofmann F, Wegener JW. The role of cGMP/cGKI signalling and Trpc channels in regulation of vascular tone. Cardiovasc Res. 2013;100:280–7.

    CAS  Google Scholar 

  101. Longden TA, Nelson MT. Vascular inward rectifier k(+) channels as external k(+) sensors in the control of cerebral blood flow. Microcirculation. 2015;22:183–96.

    CAS  Google Scholar 

  102. Mackrill JJ. Ryanodine receptor calcium channels and their partners as drug targets. Biochem Pharmacol. 2010;79:1535–43.

    CAS  Google Scholar 

  103. Mak D, McBride S, Foskett J. Regulation by Ca2+ and inositol 1,4,5-trisphosphate (InsP3) of single recombinant type 3 InsP3 receptor channels. Ca2+ activation uniquely distinguishes types 1 and 3 insp3 receptors. J Gen Physiol. 2001;117:435–46.

    CAS  Google Scholar 

  104. Mak DD, Foskett JK. Inositol 1,4,5-trisphosphate receptors in the endoplasmic reticulum: a single-channel point of view. Cell Calcium. 2014;58:67–78.

    Google Scholar 

  105. Mak DO, McBride S, Foskett JK. Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition. Proc Natl Acad Sci U S A. 1998;95:15821–5.

    CAS  Google Scholar 

  106. Mannhold R. KATP channel openers: structure-activity relationships and therapeutic potential. Med Res Rev. 2004;24:213–66.

    CAS  Google Scholar 

  107. Marrelli SP. Selective measurement of endothelial or smooth muscle [Ca(2+)](i) in pressurized/perfused cerebral arteries with fura-2. J Neurosci Methods. 2000;97:145–55.

    CAS  Google Scholar 

  108. Marrelli SP, Eckmann MS, Hunte MS. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations. Am J Physiol Heart Circ Physiol. 2003;285:H1590–9.

    CAS  Google Scholar 

  109. Marrelli SP, O’Neil RG, Brown RC, Bryan Jr RM. PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries. Am J Physiol Heart Circ Physiol. 2007;292:H1390–7.

    CAS  Google Scholar 

  110. Martin RL, Lee JH, Cribbs LL, Perez-Reyes E, Hanck DA. Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000;295:302–8.

    CAS  Google Scholar 

  111. Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem. 1997;122:498–505.

    CAS  Google Scholar 

  112. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007;104:13525–30.

    CAS  Google Scholar 

  113. McSherry IN, Spitaler MM, Takano H, Dora KA. Endothelial cell Ca2+ increases are independent of membrane potential in pressurized rat mesenteric arteries. Cell Calcium. 2005;38:23–33.

    CAS  Google Scholar 

  114. Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya T, Tiruppathi C, Minshall RD, Malik AB. 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.

    CAS  Google Scholar 

  115. Millar ID, Wang S, Brown PD, Barrand MA, Hladky SB. Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells. Pflugers Arch. 2008;456:379–91.

    CAS  Google Scholar 

  116. Miller M, Shi J, Zhu Y, Kustov M, Tian JB, Stevens A, Wu M, Xu J, Long S, Yang P, Zholos AV, Salovich JM, Weaver CD, Hopkins CR, Lindsley CW, McManus O, Li M, Zhu MX. Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels. J Biol Chem. 2011;286:33436–46.

    CAS  Google Scholar 

  117. Minami T. Calcineurin-NFAT activation and DSCR-1 auto-inhibitory loop: how is homoeostasis regulated? J Biochem. 2014;155:217–26.

    CAS  Google Scholar 

  118. Mountian I, Manolopoulos VG, De Smedt H, Parys JB, Missiaen L, Wuytack F. Expression patterns of sarco/endoplasmic reticulum Ca(2+)-ATPase and inositol 1,4,5-trisphosphate receptor isoforms in vascular endothelial cells. Cell Calcium. 1999;25:371–80.

    CAS  Google Scholar 

  119. Mountian II, Baba-Aissa F, Jonas JC, De Humbert S, Wuytack F, Parys JB. Expression of Ca(2+) transport genes in platelets and endothelial cells in hypertension. Hypertension. 2001;37:135–41.

    CAS  Google Scholar 

  120. Munaron L. Intracellular calcium, endothelial cells and angiogenesis. Recent Pat Anticancer Drug Discov. 2006;1:105–19.

    CAS  Google Scholar 

  121. Narahashi T, Tsunoo A, Yoshii M. Characterization of two types of calcium channels in mouse neuroblastoma cells. J Physiol. 1987;383:231–49.

    CAS  Google Scholar 

  122. Nelson M, Quayle J. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995;268:C799–822.

    CAS  Google Scholar 

  123. Nilius B, Droogmans G. Ion channels and their functional role in vascular endothelium. Physiol Rev. 2001;81:1415–59.

    CAS  Google Scholar 

  124. Nilius B, Droogmans G, Wondergem R. Transient receptor potential channels in endothelium: solving the calcium entry puzzle? Endothelium. 2003;10:5–15.

    CAS  Google Scholar 

  125. Nilius B, Viana F, Droogmans G. Ion channels in vascular endothelium. Annu Rev Physiol. 1997;59:145–70.

    CAS  Google Scholar 

  126. Paltauf-Doburzynska J, Posch K, Paltauf G, Graier WF. Stealth ryanodine-sensitive Ca2+ release contributes to activity of capacitative Ca2+ entry and nitric oxide synthase in bovine endothelial cells. J Physiol. 1998;513(Pt 2):369–79.

    CAS  Google Scholar 

  127. 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.

    CAS  Google Scholar 

  128. Qian X, Francis M, Kohler R, Solodushko V, Lin M, Taylor MS. Positive feedback regulation of agonist-stimulated endothelial Ca2+ dynamics by KCa3.1 channels in mouse mesenteric arteries. Arterioscler Thromb Vasc Biol. 2014;34:127–35.

    CAS  Google Scholar 

  129. Quayle JM, Nelson MT, Standen NB. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev. 1997;77:1165–232.

    CAS  Google Scholar 

  130. Quinlan KL, Naik SM, Cannon G, Armstrong CA, Bunnett NW, Ansel JC, Caughman SW. Substance P activates coincident NF-AT- and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization. J Immunol. 1999;163:5656–65.

    CAS  Google Scholar 

  131. Riddle MA, Hughes JM, Walker BR. Role of caveolin-1 in endothelial BKCa channel regulation of vasoreactivity. Am J Physiol Cell Physiol. 2011;301:C1404–14.

    CAS  Google Scholar 

  132. Rusko J, Van Slooten G, Adams DJ. Caffeine-evoked, calcium-sensitive membrane currents in rabbit aortic endothelial cells. Br J Pharmacol. 1995;115:133–41.

    CAS  Google Scholar 

  133. Saleem H, Tovey SC, Molinski TF, Taylor CW. Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor. Br J Pharmacol. 2014;171:3298–312.

    CAS  Google Scholar 

  134. Saliez J, Bouzin C, Rath G, Ghisdal P, Desjardins F, Rezzani R, Rodella LF, Vriens J, Nilius B, Feron O, Balligand JL, Dessy C. Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells. Circulation. 2008;117:1065–74.

    CAS  Google Scholar 

  135. Sandow SL, Grayson TH. Limits of isolation and culture: intact vascular endothelium and BKCa. Am J Physiol Heart Circ Physiol. 2009;297:H1–7.

    CAS  Google Scholar 

  136. Sandow SL, Hill CE. Incidence of myoendothelial gap junctions in the proximal and distal mesenteric arteries of the rat is suggestive of a role in endothelium-derived hyperpolarizing factor-mediated responses. Circ Res. 2000;86:341–6.

    CAS  Google Scholar 

  137. Sandow SL, Neylon CB, Chen MX, Garland CJ. Spatial separation of endothelial small- and intermediate-conductance calcium-activated potassium channels (K(Ca)) and connexins: possible relationship to vasodilator function? J Anat. 2006;209:689–98.

    CAS  Google Scholar 

  138. Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G. Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J Biol Chem. 2000;275:17517–26.

    CAS  Google Scholar 

  139. Schilling WP, Cabello OA, Rajan L. Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store in vascular endothelial-cells activates the agonist-sensitive Ca2+-influx pathway. Biochem J. 1992;284:521–30.

    CAS  Google Scholar 

  140. Schmidt K, Dubrovska G, Nielsen G, Fesus G, Uhrenholt TR, Hansen PB, Gudermann T, Dietrich A, Gollasch M, de Wit C, Kohler R. Amplification of EDHF-type vasodilatations in TRPC1-deficient mice. Br J Pharmacol. 2010;161:1722–33.

    CAS  Google Scholar 

  141. Senadheera S, Kim Y, Grayson TH, Toemoe S, Kochukov MY, Abramowitz J, Housley GD, Bertrand RL, Chadha PS, Bertrand PP, Murphy TV, Tare M, Birnbaumer L, Marrelli SP, Sandow SL. Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity. Cardiovasc Res. 2012;95:439–47.

    CAS  Google Scholar 

  142. Sharma NR, Davis MJ. Mechanism of substance P-induced hyperpolarization of porcine coronary artery endothelial cells. Am J Physiol. 1994;266:H156–64.

    CAS  Google Scholar 

  143. Sharma NR, Davis MJ. Substance-P-induced calcium-entry in endothelial-cells is secondary to depletion of intracellular stores. Am J Physiol Heart Circ Physiol. 1995;268:H962–73.

    CAS  Google Scholar 

  144. Si H, Heyken WT, Wolfle SE, Tysiac M, Schubert R, Grgic I, Vilianovich L, Giebing G, Maier T, Gross V, Bader M, de Wit C, Hoyer J, Kohler R. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ Res. 2006;99:537–44.

    CAS  Google Scholar 

  145. Singh I, Knezevic N, Ahmmed GU, Kini V, Malik AB, Mehta D. 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.

    CAS  Google Scholar 

  146. Smith PD, Brett SE, Luykenaar KD, Sandow SL, Marrelli SP, Vigmond EJ, Welsh DG. KIR channels function as electrical amplifiers in rat vascular smooth muscle. J Physiol. 2008;586:1147–60.

    CAS  Google Scholar 

  147. Socha MJ, Domeier TL, Behringer EJ, Segal SS. Coordination of intercellular Ca2+ signaling in endothelial cell tubes of mouse resistance arteries. Microcirculation. 2012;19:757–70.

    CAS  Google Scholar 

  148. Socha MJ, Hakim CH, Jackson WF, Segal SS. Temperature effects on morphological integrity and Ca2+ signaling in freshly isolated murine feed artery endothelial cell tubes. Am J Physiol Heart Circ Physiol. 2011;301:H773–83.

    CAS  Google Scholar 

  149. Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, Hill-Eubanks DC, Nelson MT. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336:597–601.

    CAS  Google Scholar 

  150. Sonkusare SK, Dalsgaard T, Bonev AD, Hill-Eubanks DC, Kotlikoff MI, Scott JD, Santana LF, Nelson MT. AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension. Sci Signal. 2014;7:ra66.

    Google Scholar 

  151. Straub AC, Billaud M, Johnstone SR, Best AK, Yemen S, Dwyer ST, Looft-Wilson R, Lysiak JJ, Gaston B, Palmer L, Isakson BE. Compartmentalized connexin 43S-nitrosylation/denitrosylation regulates heterocellular communication in the vessel wall. Arterioscler Thromb Vasc Biol. 2011;31:399–407.

    CAS  Google Scholar 

  152. Straub AC, Zeigler AC, Isakson BE. The myoendothelial junction: connections that deliver the message. Physiology (Bethesda). 2014;29:242–9.

    CAS  Google Scholar 

  153. Strotmann R, Schultz G, Plant TD. Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J Biol Chem. 2003;278:26541–9.

    CAS  Google Scholar 

  154. Sullivan MN, Gonzales AL, Pires PW, Bruhl A, Leo MD, Li W, Oulidi A, Boop FA, Feng Y, Jaggar JH, Welsh DG, Earley S. Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. Sci Signal. 2015;8:ra2.

    Google Scholar 

  155. Sundivakkam PC, Freichel M, Singh V, Yuan JP, Vogel SM, Flockerzi V, Malik AB, Tiruppathi C. 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.

    CAS  Google Scholar 

  156. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C. Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am J Physiol Cell Physiol. 2009;296:C403–13.

    CAS  Google Scholar 

  157. Svenningsen P, Andersen K, Thuesen A, Shin H-S, Vanhoutte P, Skøtt O, Jensen B, Hill C, Hansen PL. T-type Ca2+ channels facilitate NO-formation, vasodilatation and NO-mediated modulation of blood pressure. Pflügers Arch. 2014;466:2205–14.

    CAS  Google Scholar 

  158. Takano H, Dora KA, Spitaler MM, Garland CJ. Spreading dilatation in rat mesenteric arteries associated with calcium-independent endothelial cell hyperpolarization. J Physiol. 2004;556(pt.3):887–903.

    CAS  Google Scholar 

  159. Taylor CW, Tovey SC, Rossi AM, Lopez Sanjurjo CI, Prole DL, Rahman T. Structural organization of signalling to and from IP3 receptors. Biochem Soc Trans. 2014;42:63–70.

    CAS  Google Scholar 

  160. Taylor MS, Bonev AD, Gross TP, Eckman DM, Brayden JE, Bond CT, Adelman JP, Nelson MT. Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure. Circ Res. 2003;93:124–31.

    CAS  Google Scholar 

  161. Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: part I. J Pharmacol Exp Ther. 2008;326:432–42.

    CAS  Google Scholar 

  162. Tiruppathi C, Freichel M, Vogel SM, Paria BC, Mehta D, Flockerzi V, Malik AB. Impairment of store-operated Ca2+ entry in TRPC4(−/−) mice interferes with increase in lung microvascular permeability. Circ Res. 2002;91:70–6.

    CAS  Google Scholar 

  163. Ungvari Z, Csiszar A, Koller A. Increases in endothelial Ca(2+) activate K(Ca) channels and elicit EDHF-type arteriolar dilation via gap junctions. Am J Physiol Heart Circ Physiol. 2002;282:H1760–7.

    CAS  Google Scholar 

  164. Vaca L, Kunze DL. Depletion and refilling of intracellular Ca2+ stores induce oscillations of Ca2+ current. Am J Physiol. 1993;264:H1319–22.

    CAS  Google Scholar 

  165. Vaca L, Kunze DL. Depletion of intracellular Ca2+ stores activates a Ca2+-selective channel in vascular endothelium. Am J Physiol Cell Physiol. 1994;267:C920–5.

    CAS  Google Scholar 

  166. Vaithianathan T, Narayanan D, Asuncion-Chin MT, Jeyakumar LH, Liu J, Fleischer S, Jaggar JH, Dopico AM. Subtype identification and functional characterization of ryanodine receptors in rat cerebral artery myocytes. Am J Physiol Cell Physiol. 2010;299:C264–78.

    CAS  Google Scholar 

  167. Vinet R, Vargas FF. L- and T-type voltage-gated Ca2+ currents in adrenal medulla endothelial cells. Am J Physiol. 1999;276:H1313–22.

    CAS  Google Scholar 

  168. Vogt-Eisele AK, Weber K, Sherkheli MA, Vielhaber G, Panten J, Gisselmann G, Hatt H. Monoterpenoid agonists of TRPV3. Br J Pharmacol. 2007;151:530–40.

    CAS  Google Scholar 

  169. von Beckerath N, Dittrich M, Klieber HG, Daut J. Inwardly rectifying K+ channels in freshly dissociated coronary endothelial cells from guinea-pig heart. J Physiol. 1996;491(Pt 2):357–65.

    Google Scholar 

  170. Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A. 2004;101:396–401.

    CAS  Google Scholar 

  171. Wagner II LE, Yule DI. Differential regulation of the InsP(3) receptor type-1 and -2 single channel properties by InsP(3), Ca(2)(+) and ATP. J Physiol. 2012;590:3245–59.

    CAS  Google Scholar 

  172. Wang H-R, Wu M, Yu H, Long S, Stevens A, Engers DW, Sackin H, Daniels JS, Dawson ES, Hopkins CR, Lindsley CW, Li M, McManus OB. Selective inhibition of the Kir2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR, and pharmacological characterization of ML133. ACS Chem Biol. 2011;6:845–56.

    CAS  Google Scholar 

  173. Wang XL, Ye D, Peterson TE, Cao S, Shah VH, Katusic ZS, Sieck GC, Lee HC. Caveolae targeting and regulation of large conductance Ca(2+)-activated K+ channels in vascular endothelial cells. J Biol Chem. 2005;280:11656–64.

    CAS  Google Scholar 

  174. Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, Vriens J, Cairns W, Wissenbach U, Prenen J, Flockerzi V, Droogmans G, Benham CD, Nilius B. Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem. 2002;277:13569–77.

    CAS  Google Scholar 

  175. Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem. 2002;277:47044–51.

    CAS  Google Scholar 

  176. Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H. International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol Rev. 2005;57:463–72.

    CAS  Google Scholar 

  177. Wei Z, Manevich Y, Al-Mehdi AB, Chatterjee S, Fisher AB. Ca2+ flux through voltage-gated channels with flow cessation in pulmonary microvascular endothelial cells. Microcirculation. 2004;11:517–26.

    CAS  Google Scholar 

  178. Westcott EB, Goodwin EL, Segal SS, Jackson WF. Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles. J Physiol. 2012;590:1849–69.

    CAS  Google Scholar 

  179. Wu LJ, Sweet TB, Clapham DE. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev. 2010;62:381–404.

    CAS  Google Scholar 

  180. Wu S, Haynes Jr J, Taylor JT, Obiako BO, Stubbs JR, Li M, Stevens T. Cav3.1 (alpha1G) T-type Ca2+ channels mediate vaso-occlusion of sickled erythrocytes in lung microcirculation. Circ Res. 2003;93:346–53.

    CAS  Google Scholar 

  181. Wulff H, Kohler R. Endothelial small-conductance and intermediate-conductance KCa channels: an update on their pharmacology and usefulness as cardiovascular targets. J Cardiovasc Pharmacol. 2013;61:102–12.

    CAS  Google Scholar 

  182. Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, Maylie J, Adelman JP. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature. 1998;395:503–7.

    CAS  Google Scholar 

  183. Xu W, Lipscombe D. Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci. 2001;21:5944–51.

    CAS  Google Scholar 

  184. Yeon SI, Kim JY, Yeon DS, Abramowitz J, Birnbaumer L, Muallem S, Lee YH. Transient receptor potential canonical type 3 channels control the vascular contractility of mouse mesenteric arteries. PLoS One. 2014;9:e110413.

    Google Scholar 

  185. Zalk R, Lehnart S, Marks A. Modulation of the ryanodine receptor and intracellular calcium. Annu Rev Biochem. 2007;76:367–85.

    CAS  Google Scholar 

  186. Zaritsky JJ, Eckman DM, Wellman GC, Nelson MT, Schwarz TL. Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation. Circ Res. 2000;87:160–6.

    CAS  Google Scholar 

  187. Zhang DX, Mendoza SA, Bubolz AH, Mizuno A, Ge ZD, Li R, Warltier DC, Suzuki M, Gutterman DD. Transient receptor potential vanilloid type 4-deficient mice exhibit impaired endothelium-dependent relaxation induced by acetylcholine in vitro and in vivo. Hypertension. 2009;53:532–8.

    CAS  Google Scholar 

  188. Zheng W, Rampe D, Triggle DJ. Pharmacological, radioligand binding, and electrophysiological characteristics of FPL 64176, a novel nondihydropyridine Ca2+ channel activator, in cardiac and vascular preparations. Mol Pharmacol. 1991;40:734–41.

    CAS  Google Scholar 

  189. Zhou C, Chen H, Lu F, Sellak H, Daigle JA, Alexeyev MF, Xi Y, Ju J, van Mourik JA, Wu S. Cav3.1 (alpha1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2007;292:L833–44.

    CAS  Google Scholar 

  190. Zhou M-H, Zheng H, Si H, Jin Y, Peng JM, He L, Zhou Y, Muñoz-Garay C, Zawieja DC, Kuo L, Peng X, Zhang SL. 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.

    CAS  Google Scholar 

  191. Ziegelstein RC, Spurgeon HA, Pili R, Passaniti A, Cheng L, Corda S, Lakatta EG, Capogrossi MC. A functional ryanodine-sensitive intracellular Ca2+ store is present in vascular endothelial cells. Circ Res. 1994;74:151–6.

    CAS  Google Scholar 

  192. Zucchi R, Ronca-Testoni S. The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states. Pharmacol Rev. 1997;49:1–51.

    CAS  Google Scholar 

Download references

Acknowledgements

Supported NIH grants RO1-HL32469, RO1-HL086483 and PO1-HL070687.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William F. Jackson .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Jackson, W.F. (2016). Endothelial Cell Ion Channel Expression and Function in Arterioles and Resistance Arteries. 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_1

Download citation

Publish with us

Policies and ethics