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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1415-1459
Copyright ©2001 by the American Physiological Society
Department of Physiology, KU Leuven, Campus Gasthuisberg, Leuven, Belgium
Nilius, Bernd and
Guy Droogmans.
Ion Channels and Their Functional Role in Vascular
Endothelium. Physiol. Rev. 81: 1415-1459, 2001.
Endothelial cells (EC) form a unique
signal-transducing surface in the vascular system. The abundance of
ion channels in the plasma membrane of these nonexcitable cells has
raised questions about their functional role. This review presents
evidence for the involvement of ion channels in endothelial cell
functions controlled by intracellular Ca2+ signals, such as
the production and release of many vasoactive factors, e.g., nitric
oxide and PGI2. In addition, ion channels may be involved
in the regulation of the traffic of macromolecules by endocytosis,
transcytosis, the biosynthetic-secretory pathway, and exocytosis,
e.g., tissue factor pathway inhibitor, von Willebrand factor, and
tissue plasminogen activator. Ion channels are also involved in
controlling intercellular permeability, EC proliferation, and
angiogenesis. These functions are supported or triggered via ion
channels, which either provide Ca2+-entry pathways or
stabilize the driving force for Ca2+ influx through these
pathways. These Ca2+-entry pathways comprise
agonist-activated nonselective Ca2+-permeable cation
channels, cyclic nucleotide-activated nonselective cation channels,
and store-operated Ca2+ channels or capacitative
Ca2+ entry. At least some of these channels appear to be
expressed by genes of the trp family. The driving force for
Ca2+ entry is mainly controlled by large-conductance
Ca2+-dependent BKCa channels (slo),
inwardly rectifying K+ channels (Kir2.1), and at least two
types of Cl 
channels, i.e., the
Ca2+-activated Cl channel and the
housekeeping, volume-regulated anion channel (VRAC). In addition to
their essential function in Ca2+ signaling, VRAC channels
are multifunctional, operate as a transport pathway for amino acids and
organic osmolytes, and are possibly involved in endothelial cell
proliferation and angiogenesis. Finally, we have also highlighted the
role of ion channels as mechanosensors in EC. Plasmalemmal ion channels
may signal rapid changes in hemodynamic forces, such as shear stress
and biaxial tensile stress, but also changes in cell shape and cell
volume to the cytoskeleton and the intracellular machinery for
metabolite traffic and gene expression.
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A. Sato, K. Terata, H. Miura, K. Toyama, F. R. Loberiza Jr., O. A. Hatoum, T. Saito, I. Sakuma, and D. D. Gutterman Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1633 - H1640. [Abstract] [Full Text] [PDF]
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D. M. Cohen SRC family kinases in cell volume regulation Am J Physiol Cell Physiol, March 1, 2005; 288(3): C483 - C493. [Abstract] [Full Text] [PDF]
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 M. D. Burmester, K.-D. Schluter, J. Daut, and P. J. Hanley Enantioselective Actions of Bupivacaine and Ropivacaine on Coronary Vascular Resistance at Cardiotoxic Concentrations Anesth. Analg., March 1, 2005; 100(3): 707 - 712. [Abstract] [Full Text] [PDF]
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R. Dwivedi, S. Saha, P.J. Chowienczyk, and J.M. Ritter Block of Inward Rectifying K+ Channels (KIR) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): e7 - e9. [Abstract] [Full Text] [PDF]
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X. Wang, M. D. Hollenberg, and R. Loutzenhiser Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2 Am J Physiol Renal Physiol, January 1, 2005; 288(1): F65 - F75. [Abstract] [Full Text] [PDF]
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D. Mehta, J. Bhattacharya, M. A. Matthay, and A. B. Malik Integrated control of lung fluid balance Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1081 - L1090. [Abstract] [Full Text] [PDF]
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B. C. Paria, S. M. Vogel, G. U. Ahmmed, S. Alamgir, J. Shroff, A. B. Malik, and C. Tiruppathi Tumor necrosis factor-{alpha}-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1303 - L1313. [Abstract] [Full Text] [PDF]
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H. Jia, A. Bagherzadeh, R. Bicknell, M. R. Duchen, D. Liu, and I. Zachary Vascular Endothelial Growth Factor (VEGF)-D and VEGF-A Differentially Regulate KDR-mediated Signaling and Biological Function in Vascular Endothelial Cells J. Biol. Chem., August 20, 2004; 279(34): 36148 - 36157. [Abstract] [Full Text] [PDF]
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S. Sultan, M. Gosling, S. Abu-Hayyeh, N. Carey, and J. T. Powell Flow-dependent increase of ICAM-1 on saphenous vein endothelium is sensitive to apamin Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H22 - H28. [Abstract] [Full Text] [PDF]
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S. F. B. Tomassen, D. Fekkes, H. R. de Jonge, and B. C. Tilly Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1417 - C1422. [Abstract] [Full Text] [PDF]
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T. Duza and I. H. Sarelius Localized transient increases in endothelial cell Ca2+ in arterioles in situ: implications for coordination of vascular function Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2322 - H2331. [Abstract] [Full Text] [PDF]
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M. Suzuki and A. Mizuno A Novel Human Cl- Channel Family Related to Drosophila flightless Locus J. Biol. Chem., May 21, 2004; 279(21): 22461 - 22468. [Abstract] [Full Text] [PDF]
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G. U. Ahmmed, D. Mehta, S. Vogel, M. Holinstat, B. C. Paria, C. Tiruppathi, and A. B. Malik Protein Kinase C{alpha} Phosphorylates the TRPC1 Channel and Regulates Store-operated Ca2+ Entry in Endothelial Cells J. Biol. Chem., May 14, 2004; 279(20): 20941 - 20949. [Abstract] [Full Text] [PDF]
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S. Yamamoto-Mizuma, G.-X. Wang, and J. R. Hume P2Y purinergic receptor regulation of CFTR chloride channels in mouse cardiac myocytes J. Physiol., May 1, 2004; 556(3): 727 - 737. [Abstract] [Full Text] [PDF]
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 A. Dalrymple, D. M. Slater, L. Poston, and R. M. Tribe Physiological Induction of Transient Receptor Potential Canonical Proteins, Calcium Entry Channels, in Human Myometrium: Influence of Pregnancy, Labor, and Interleukin-1{beta} J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1291 - 1300. [Abstract] [Full Text] [PDF]
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T. M. Pocock, R. R. Foster, and D. O. Bates Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1015 - H1026. [Abstract] [Full Text] [PDF]
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D. F. Alvarez, E.-A. B. Gjerde, and M. I. Townsley Role of EETs in regulation of endothelial permeability in rat lung Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L445 - L451. [Abstract] [Full Text] [PDF]
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 P. V. Lovell, J. T. King, and D. P. McCobb Acute Modulation of Adrenal Chromaffin Cell BK Channel Gating and Cell Excitability by Glucocorticoids J Neurophysiol, January 1, 2004; 91(1): 561 - 570. [Abstract] [Full Text]
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G. H. Seol, S. C. Ahn, J. A. Kim, B. Nilius, and S. H. Suh Inhibition of endothelium-dependent vasorelaxation by extracellular K+: a novel controlling signal for vascular contractility Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H329 - H339. [Abstract] [Full Text] [PDF]
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R. Ma, D. Rundle, J. Jacks, M. Koch, T. Downs, and L. Tsiokas Inhibitor of Myogenic Family, a Novel Suppressor of Store-operated Currents through an Interaction with TRPC1 J. Biol. Chem., December 26, 2003; 278(52): 52763 - 52772. [Abstract] [Full Text] [PDF]
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E. van Bavel Shear stress and intermediate-conductance calcium-activated potassium channels Cardiovasc Res, December 1, 2003; 60(3): 457 - 459. [Full Text] [PDF]
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S. Brakemeier, A. Kersten, I. Eichler, I. Grgic, A. Zakrzewicz, H. Hopp, R. Kohler, and J. Hoyer Shear stress-induced up-regulation of the intermediate-conductance Ca2+-activated K+ channel in human endothelium Cardiovasc Res, December 1, 2003; 60(3): 488 - 496. [Abstract] [Full Text] [PDF]
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C. R. W. Kuhlmann, M. Schafer, F. Li, T. Sawamura, H. Tillmanns, B. Waldecker, and J. Wiecha Modulation of endothelial Ca2+-activated K+ channels by oxidized LDL and its contribution to endothelial proliferation Cardiovasc Res, December 1, 2003; 60(3): 626 - 634. [Abstract] [Full Text] [PDF]
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S. P. Marrelli, M. S. Eckmann, and M. S. Hunte Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1590 - H1599. [Abstract] [Full Text] [PDF]
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B. C. Paria, A. B. Malik, A. M. Kwiatek, A. Rahman, M. J. May, S. Ghosh, and C. Tiruppathi Tumor Necrosis Factor-{alpha} Induces Nuclear Factor-{kappa}B-dependent TRPC1 Expression in Endothelial Cells J. Biol. Chem., September 26, 2003; 278(39): 37195 - 37203. [Abstract] [Full Text] [PDF]
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X. Wang, G. Trottier, and R. Loutzenhiser Determinants of renal afferent arteriolar actions of bradykinin: evidence that multiple pathways mediate responses attributed to EDHF Am J Physiol Renal Physiol, September 1, 2003; 285(3): F540 - F549. [Abstract] [Full Text] [PDF]
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D. Mehta, G. U. Ahmmed, B. C. Paria, M. Holinstat, T. Voyno-Yasenetskaya, C. Tiruppathi, R. D. Minshall, and A. B. Malik 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., August 29, 2003; 278(35): 33492 - 33500. [Abstract] [Full Text] [PDF]
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S. Wu, J. Haynes Jr, J. T. Taylor, B. O. Obiako, J. R. Stubbs, M. Li, and T. Stevens Cav3.1 ({alpha}1G) T-Type Ca2+ Channels Mediate Vaso-Occlusion of Sickled Erythrocytes in Lung Microcirculation Circ. Res., August 22, 2003; 93(4): 346 - 353. [Abstract] [Full Text] [PDF]
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O. Kann, R. Kovacs, and U. Heinemann Metabotropic Receptor-Mediated Ca2+ Signaling Elevates Mitochondrial Ca2+ and Stimulates Oxidative Metabolism in Hippocampal Slice Cultures J Neurophysiol, August 1, 2003; 90(2): 613 - 621. [Abstract] [Full Text] [PDF]
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S. Budel, I. S. Bartlett, and S. S. Segal Homocellular Conduction Along Endothelium and Smooth Muscle of Arterioles in Hamster Cheek Pouch: Unmasking an NO Wave Circ. Res., July 11, 2003; 93(1): 61 - 68. [Abstract] [Full Text] [PDF]
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