| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Integrative Physiology |
From the Department of Pharmacology, The University of Illinois, Chicago, Ill; and Universitat des Saarlandes (M.F., V.F.), Institut fur Pharmakologie und Toxikologie, Homburg, Germany.
Correspondence to Asrar B. Malik, PhD, Distinguished Professor and Head, Dept of Pharmacology M/C868, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, Chicago, IL 60612. E-mail abmalik{at}uic.edu
We investigated the possibility that the TRPC gene family of putative store-operated Ca2+ entry channels contributes to the increase in microvascular endothelial permeability by prolonging the rise in intracellular Ca2+ signaling. Studies were made in wild-type (wt) and TRPC4 knockout (TRPC4-/-) mice and lung vascular endothelial cells (LECs) isolated from these animals. RT-PCR showed expression of TRPC1, TRPC3, TRPC4, and TRPC6 mRNA in wt LECs, but TRPC4 mRNA expression was not detected in TRPC4-/- LECs. We studied the response to thrombin because it is known to increase endothelial permeability by the activation of G protein-coupled proteinase-activated receptor-1 (PAR-1). In wt LECs, thrombin or PAR-1 agonist peptide (TFLLRNPNDK-NH2) resulted in a prolonged Ca2+ transient secondary to influx of Ca2+. Ca2+ influx activated by thrombin was blocked by La3+ (1 µmol/L). In TRPC4-/- LECs, thrombin or TFLLRNPNDK-NH2 produced a similar initial increase of intracellular Ca2+ secondary to Ca2+ store depletion, but Ca2+ influx induced by these agonists was drastically reduced. The defect in Ca2+ influx in TRPC4-/- endothelial cells was associated with lack of thrombin-induced actin-stress fiber formation and a reduced endothelial cell retraction response. In isolated-perfused mouse lungs, the PAR-1 agonist peptide increased microvessel filtration coefficient (Kf,c), a measure of vascular permeability, by a factor of 2.8 in wt and 1.4 in TRPC4-/-; La3+ (1 µmol/L) addition to wt lung perfusate reduced the agonist effect to that observed in TRPC4-/-. These results show that TRPC4-dependent Ca2+ entry in mouse LECs is a key determinant of increased microvascular permeability.
Key Words: mouse lung endothelial cells thrombin-induced Ca2+ influx TRPC4 knockout lung microvascular permeability
This article has been cited by other articles:
![]() |
A. Graziani, M. Poteser, W.-M. Heupel, H. Schleifer, M. Krenn, D. Drenckhahn, C. Romanin, W. Baumgartner, and K. Groschner Cell-Cell Contact Formation Governs Ca2+ Signaling by TRPC4 in the Vascular Endothelium: EVIDENCE FOR A REGULATORY TRPC4-{beta}-CATENIN INTERACTION J. Biol. Chem., February 5, 2010; 285(6): 4213 - 4223. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Li, M. Xiang, Y. Yuan, G. Xiao, J. Zhang, Y. Jiang, Y. Vodovotz, T. R. Billiar, M. A. Wilson, and J. Fan Hemorrhagic shock augments lung endothelial cell activation: role of temporal alterations of TLR4 and TLR2 Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1670 - R1680. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Chun and A. Prince Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration J. Leukoc. Biol., November 1, 2009; 86(5): 1135 - 1144. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. C. Sundivakkam, A. M. Kwiatek, T. T. Sharma, R. D. Minshall, A. B. Malik, and C. Tiruppathi 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, March 1, 2009; 296(3): C403 - C413. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Abramowitz and L. Birnbaumer Physiology and pathophysiology of canonical transient receptor potential channels FASEB J, February 1, 2009; 23(2): 297 - 328. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Bair, P. B. Thippegowda, M. Freichel, N. Cheng, R. D. Ye, S. M. Vogel, Y. Yu, V. Flockerzi, A. B. Malik, and C. Tiruppathi Ca2+ Entry via TRPC Channels Is Necessary for Thrombin-induced NF-{kappa}B Activation in Endothelial Cells through AMP-activated Protein Kinase and Protein Kinase C{delta} J. Biol. Chem., January 2, 2009; 284(1): 563 - 574. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. S. Sacks, A. L. Firth, C. V. Remillard, N. Agange, J. Yau, E. A. Ko, and J. X.-J. Yuan Thrombin-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2008; 295(6): L1048 - L1055. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. F. Abdullaev, J. M. Bisaillon, M. Potier, J. C. Gonzalez, R. K. Motiani, and M. Trebak Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry Important for Endothelial Cell Proliferation Circ. Res., November 21, 2008; 103(11): 1289 - 1299. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. T. Cheng, X. Liu, H. L. Ong, and I. S. Ambudkar Functional Requirement for Orai1 in Store-operated TRPC1-STIM1 Channels J. Biol. Chem., May 9, 2008; 283(19): 12935 - 12940. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. A. Maniatis, V. Shinin, D. E. Schraufnagel, S. Okada, S. M. Vogel, A. B. Malik, and R. D. Minshall Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1-/- mice Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L865 - L873. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-i. Otsuguro, J. Tang, Y. Tang, R. Xiao, M. Freichel, V. Tsvilovskyy, S. Ito, V. Flockerzi, M. X. Zhu, and A. V. Zholos Isoform-specific Inhibition of TRPC4 Channel by Phosphatidylinositol 4,5-Bisphosphate J. Biol. Chem., April 11, 2008; 283(15): 10026 - 10036. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. F. Odell, D. F. Van Helden, and J. L. Scott The Spectrin Cytoskeleton Influences the Surface Expression and Activation of Human Transient Receptor Potential Channel 4 Channels J. Biol. Chem., February 15, 2008; 283(7): 4395 - 4407. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Dietrich and T. Gudermann Another TRP to Endothelial Dysfunction: TRPM2 and Endothelial Permeability Circ. Res., February 15, 2008; 102(3): 275 - 277. [Full Text] [PDF] |
||||
![]() |
B. Troyanovsky, D. F. Alvarez, J. A. King, and K. L. Schaphorst Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L266 - L275. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Wimmers and O. Strauss Basal Calcium Entry in Retinal Pigment Epithelial Cells Is Mediated by TRPC Channels Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5767 - 5772. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Zhang, H. Dong, L. J. Rubin, and J. X.-J. Yuan Upregulation of Na+/Ca2+ exchanger contributes to the enhanced Ca2+ entry in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2297 - C2305. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kiselyov, A. Soyombo, and S. Muallem TRPpathies J. Physiol., February 1, 2007; 578(3): 641 - 653. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Y. Kim, W. Zeng, K. Kiselyov, J. P. Yuan, M. H. Dehoff, K. Mikoshiba, P. F. Worley, and S. Muallem Homer 1 Mediates Store- and Inositol 1,4,5-Trisphosphate Receptor-dependent Translocation and Retrieval of TRPC3 to the Plasma Membrane J. Biol. Chem., October 27, 2006; 281(43): 32540 - 32549. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. F. Alvarez, J. A. King, D. Weber, E. Addison, W. Liedtke, and M. I. Townsley Transient Receptor Potential Vanilloid 4-Mediated Disruption of the Alveolar Septal Barrier: A Novel Mechanism of Acute Lung Injury Circ. Res., October 27, 2006; 99(9): 988 - 995. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Kwiatek, R. D. Minshall, D. R. Cool, R. A. Skidgel, A. B. Malik, and C. Tiruppathi Caveolin-1 Regulates Store-Operated Ca2+ Influx by Binding of Its Scaffolding Domain to Transient Receptor Potential Channel-1 in Endothelial Cells Mol. Pharmacol., October 1, 2006; 70(4): 1174 - 1183. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-W. Cheng, A.F. James, R.R. Foster, J.C. Hancox, and D.O. Bates VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1768 - 1776. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Paria, A. M. Bair, J. Xue, Y. Yu, A. B. Malik, and C. Tiruppathi Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-{kappa}B Activation in Endothelial Cells J. Biol. Chem., July 28, 2006; 281(30): 20715 - 20727. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sours, J. Du, S. Chu, M. Ding, X. J. Zhou, and R. Ma Expression of canonical transient receptor potential (TRPC) proteins in human glomerular mesangial cells Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1507 - F1515. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Poteser, A. Graziani, C. Rosker, P. Eder, I. Derler, H. Kahr, M. X. Zhu, C. Romanin, and K. Groschner TRPC3 and TRPC4 Associate to Form a Redox-sensitive Cation Channel: EVIDENCE FOR EXPRESSION OF NATIVE TRPC3-TRPC4 HETEROMERIC CHANNELS IN ENDOTHELIAL CELLS J. Biol. Chem., May 12, 2006; 281(19): 13588 - 13595. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Broman, P. Kouklis, X. Gao, R. Ramchandran, R. F. Neamu, R. D. Minshall, and A. B. Malik Cdc42 Regulates Adherens Junction Stability and Endothelial Permeability by Inducing {alpha}-Catenin Interaction With the Vascular Endothelial Cadherin Complex Circ. Res., January 6, 2006; 98(1): 73 - 80. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. F. Odell, J. L. Scott, and D. F. Van Helden Epidermal Growth Factor Induces Tyrosine Phosphorylation, Membrane Insertion, and Activation of Transient Receptor Potential Channel 4 J. Biol. Chem., November 11, 2005; 280(45): 37974 - 37987. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. F. Alvarez, J. A. King, and M. I. Townsley Resistance to Store Depletion-induced Endothelial Injury in Rat Lung after Chronic Heart Failure Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1153 - 1160. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Yao and C. J. Garland Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels Circ. Res., October 28, 2005; 97(9): 853 - 863. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Freichel, R. Vennekens, J. Olausson, S. Stolz, S. E Philipp, P. Weissgerber, and V. Flockerzi Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies J. Physiol., August 15, 2005; 567(1): 59 - 66. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Nilius, T. Voets, and J. Peters TRP Channels in Disease Sci. Signal., August 2, 2005; 2005(295): re8 - re8. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Jho, D. Mehta, G. Ahmmed, X.-P. Gao, C. Tiruppathi, M. Broman, and A. B. Malik Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca2 Influx Circ. Res., June 24, 2005; 96(12): 1282 - 1290. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Roos, P. J. DiGregorio, A. V. Yeromin, K. Ohlsen, M. Lioudyno, S. Zhang, O. Safrina, J. A. Kozak, S. L. Wagner, M. D. Cahalan, et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function J. Cell Biol., May 9, 2005; 169(3): 435 - 445. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. V. Remillard and J. X.-J. Yuan PGE2 and PAR-1 in pulmonary fibrosis: a case of biting the hand that feeds you? Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L789 - L792. [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
S. Zhang, C. V. Remillard, I. Fantozzi, and J. X.-J. Yuan ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1192 - C1201. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wu, T. K. Zagranichnaya, G. T. Gurda, E. M. Eves, and M. L. Villereal A TRPC1/TRPC3-mediated Increase in Store-operated Calcium Entry Is Required for Differentiation of H19-7 Hippocampal Neuronal Cells J. Biol. Chem., October 15, 2004; 279(42): 43392 - 43402. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Winter, S. S. Shasby, D. R. Ries, and D. M. Shasby Histamine selectively interrupts VE-cadherin adhesion independently of capacitive calcium entry Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L816 - L823. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. LEE, C.-H. CHO, S.-J. HWANG, H.-H. CHOI, K.-T. KIM, S. Y. AHN, J.-H. KIM, J.-L. OH, G. M. LEE, and G. Y. KOH Biological characterization of angiopoietin-3 and angiopoietin-4 FASEB J, August 1, 2004; 18(11): 1200 - 1208. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wang, J. L. Pluznick, P. Wei, B. J. Padanilam, and S. C. Sansom TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells Am J Physiol Cell Physiol, August 1, 2004; 287(2): C357 - C364. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Glass and D. O. Bates The role of endothelial cell Ca2+ store release in the regulation of microvascular permeability in vivo Exp Physiol, July 1, 2004; 89(4): 343 - 351. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
B. Geldziler, P. Kadandale, and A. Singson Molecular genetic approaches to studying fertilization in model systems Reproduction, April 1, 2004; 127(4): 409 - 416. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. S. Facemire, P. J. Mohler, and W. J. Arendshorst Expression and relative abundance of short transient receptor potential channels in the rat renal microcirculation Am J Physiol Renal Physiol, March 1, 2004; 286(3): F546 - F551. [Abstract] [Full Text] |
||||
![]() |
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] |
||||
![]() |
P. Kouklis, M. Konstantoulaki, S. Vogel, M. Broman, and A. B. Malik Cdc42 Regulates the Restoration of Endothelial Barrier Function Circ. Res., February 6, 2004; 94(2): 159 - 166. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Nilius, J. Vriens, J. Prenen, G. Droogmans, and T. Voets TRPV4 calcium entry channel: a paradigm for gating diversity Am J Physiol Cell Physiol, February 1, 2004; 286(2): C195 - C205. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Parker and M. I. Townsley Evaluation of lung injury in rats and mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L231 - L246. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Fantozzi, S. Zhang, O. Platoshyn, C. V. Remillard, R. T. Cowling, and J. X.-J. Yuan Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1233 - L1245. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. V. Usatyuk, V. P. Fomin, S. Shi, J. G. N. Garcia, K. Schaphorst, and V. Natarajan Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell barrier function Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1006 - L1017. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
H. Watanabe, J. Vriens, S. H. Suh, C. D. Benham, G. Droogmans, and B. Nilius Heat-evoked Activation of TRPV4 Channels in a HEK293 Cell Expression System and in Native Mouse Aorta Endothelial Cells J. Biol. Chem., November 27, 2002; 277(49): 47044 - 47051. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Birnbaumer TRPC4 Knockout Mice: The Coming of Age of TRP Channels as Gates of Calcium Entry Responsible for Cellular Responses Circ. Res., July 12, 2002; 91(1): 1 - 3. [Full Text] [PDF] |
||||
|
Circulation Research Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2002 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |