Skip to main content

Advertisement

SpringerLink
Log in

Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration

  • Ion channels, Receptors and Transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Airway smooth muscle cell (ASMC) remodeling contributes to the structural changes in the airways that are central to the clinical manifestations of asthma. Ca2+ signals play an important role in ASMC remodeling through control of ASMC migration and hypertrophy/proliferation. Upregulation of STIM1 and Orai1 proteins, the molecular components of the store-operated Ca2+ entry (SOCE) pathway, has recently emerged as an important mediator of vascular remodeling. However, the potential upregulation of STIM1 and Orai1 in asthmatic airways remains unknown. An important smooth muscle migratory agonist with major contributions to ASMC remodeling is the platelet-derived growth factor (PDGF). Nevertheless, the Ca2+ entry route activated by PDGF in ASMC remains elusive. Here, we show that STIM1 and Orai1 protein levels are greatly upregulated in ASMC isolated from ovalbumin-challenged asthmatic mice, compared to control mice. Furthermore, we show that PDGF activates a Ca2+ entry pathway in rat primary ASMC that is pharmacologically reminiscent of SOCE. Molecular knockdown of STIM1 and Orai1 proteins inhibited PDGF-activated Ca2+ entry in these cells. Whole-cell patch clamp recordings revealed the activation of Ca2+ release-activated Ca2+ (CRAC) current by PDGF in ASMC. These CRAC currents were abrogated upon either STIM1 or Orai1 knockdown. We show that either STIM1 or Orai1 knockdown significantly inhibited ASMC proliferation and chemotactic migration in response to PDGF. These results implicate STIM1 and Orai1 in PDGF-induced ASMC proliferation and migration and suggest the potential use of STIM1 and Orai1 as targets for ASMC remodeling during asthma.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Abdullaev IF, Bisaillon JM, Potier M, Gonzalez JC, Motiani RK, Trebak M (2008) Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res 103(11):1289–1299. doi:10.1161/01.RES.0000338496.95579.56

    Article  PubMed  CAS  Google Scholar 

  2. Bai TR (2010) Evidence for airway remodeling in chronic asthma. Curr Opin Allergy Clin Immunol 10(1):82–86

    PubMed  Google Scholar 

  3. Beech DJ (2007) Ion channel switching and activation in smooth-muscle cells of occlusive vascular diseases. Biochem Soc Trans 35(Pt 5):890–894. doi:10.1042/BST0350890

    PubMed  CAS  Google Scholar 

  4. Bentley JK, Hershenson MB (2008) Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration. Proc Am Thorac Soc 5(1):89–96

    Article  PubMed  CAS  Google Scholar 

  5. Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA (2008) Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol 295(3):C779–C790. doi:10.1152/ajpcell.00173.2008

    Article  PubMed  CAS  Google Scholar 

  6. Berridge MJ (2006) Remodelling Ca2+ signalling systems and cardiac hypertrophy. Biochem Soc Trans 34(Pt 2):228–231

    PubMed  CAS  Google Scholar 

  7. Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 1793:933–940

    Article  PubMed  CAS  Google Scholar 

  8. Berridge MJ (2008) Smooth muscle cell calcium activation mechanisms. J Physiol 586(Pt 21):5047–5061

    Article  PubMed  CAS  Google Scholar 

  9. Betsholtz C (2004) Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 15(4):215–228

    Article  PubMed  CAS  Google Scholar 

  10. Bird GS, Aziz O, Lievremont JP, Wedel BJ, Trebak M, Vazquez G, Putney JW Jr (2004) Mechanisms of phospholipase C-regulated calcium entry. Curr Mol Med 4(3):291–301

    Article  PubMed  CAS  Google Scholar 

  11. Bisaillon JM, Motiani RK, Gonzalez-Cobos JC, Potier M, Halligan KE, Alzawahra WF, Barroso M, Singer HA, Jourd’heuil D, Trebak M (2010) Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration. Am J Physiol Cell Physiol 298(5):C993–C1005

    Article  PubMed  CAS  Google Scholar 

  12. Bobe R, Hadri L, Lopez JJ, Sassi Y, Atassi F, Karakikes I, Liang L, Limon I, Lompre AM, Hatem SN, Hajjar RJ, Lipskaia L (2011) SERCA2a controls the mode of agonist-induced intracellular Ca(2+) signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells. J Mol Cell Cardiol 50:621–33

    Article  PubMed  CAS  Google Scholar 

  13. Broad LM, Cannon TR, Taylor CW (1999) A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J Physiol 517(Pt 1):121–134

    Article  PubMed  CAS  Google Scholar 

  14. Carlin SM, Roth M, Black JL (2003) Urokinase potentiates PDGF-induced chemotaxis of human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 284(6):L1020–L1026

    PubMed  CAS  Google Scholar 

  15. Cheong A, Bingham AJ, Li J, Kumar B, Sukumar P, Munsch C, Buckley NJ, Neylon CB, Porter KE, Beech DJ, Wood IC (2005) Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation. Mol Cell 20(1):45–52

    Article  PubMed  CAS  Google Scholar 

  16. Ebina M, Takahashi T, Chiba T, Motomiya M (1993) Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study. Am Rev Respir Dis 148(3):720–726

    Article  PubMed  CAS  Google Scholar 

  17. Ebina M, Yaegashi H, Chiba R, Takahashi T, Motomiya M, Tanemura M (1990) Hyperreactive site in the airway tree of asthmatic patients revealed by thickening of bronchial muscles. A morphometric study. Am Rev Respir Dis 141(5 Pt 1):1327–1332

    PubMed  CAS  Google Scholar 

  18. Eder P, Molkentin JD (2011) TRPC channels as effectors of cardiac hypertrophy. Circ Res 108(2):265–272

    Article  PubMed  CAS  Google Scholar 

  19. Edwards JN, Friedrich O, Cully TR, von Wegner F, Murphy RM, Launikonis BS (2010) Upregulation of store-operated Ca2+ entry in dystrophic mdx mouse muscle. Am J Physiol Cell Physiol 299(1):C42–C50

    Article  PubMed  CAS  Google Scholar 

  20. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441(7090):179–185

    Article  PubMed  CAS  Google Scholar 

  21. Gabazza EC, Taguchi O, Tamaki S, Takeya H, Kobayashi H, Yasui H, Kobayashi T, Hataji O, Urano H, Zhou H, Suzuki K, Adachi Y (1999) Thrombin in the airways of asthmatic patients. Lung 177(4):253–262

    Article  PubMed  CAS  Google Scholar 

  22. Graham SJ, Black MJ, Soboloff J, Gill DL, Dziadek MA, Johnstone LS (2009) Stim1, an endoplasmic reticulum Ca2+ sensor, negatively regulates 3 T3-L1 pre-adipocyte differentiation. Differentiation: Res Biol Divers 77(3):239–247

    Article  CAS  Google Scholar 

  23. Halwani R, Al-Muhsen S, Hamid Q (2010) Airway remodeling in asthma. Curr Opin Pharmacol 10(3):236–245

    Article  PubMed  CAS  Google Scholar 

  24. Hirst SJ, Martin JG, Bonacci JV, Chan V, Fixman ED, Hamid QA, Herszberg B, Lavoie JP, McVicker CG, Moir LM, Nguyen TT, Peng Q, Ramos-Barbon D, Stewart AG (2004) Proliferative aspects of airway smooth muscle. J Allergy Clin Immunol 114(2 Suppl):S2–S17

    Article  PubMed  CAS  Google Scholar 

  25. Holtzman MJ, Byers DE, Benoit LA, Battaile JT, You Y, Agapov E, Park C, Grayson MH, Kim EY, Patel AC (2009) Immune pathways for translating viral infection into chronic airway disease. Adv Immunol 102:245–276

    Article  PubMed  CAS  Google Scholar 

  26. House SJ, Potier M, Bisaillon J, Singer HA, Trebak M (2008) The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease. Pflugers Arch 456(5):769–785. doi:10.1007/s00424-008-0491-8

    Article  PubMed  CAS  Google Scholar 

  27. Hu Q, Zheng G, Zweier JL, Deshpande S, Irani K, Ziegelstein RC (2000) NADPH oxidase activation increases the sensitivity of intracellular Ca2+ stores to inositol 1,4,5-trisphosphate in human endothelial cells. J Biol Chem 275(21):15749–15757

    Article  PubMed  CAS  Google Scholar 

  28. Ito I, Fixman ED, Asai K, Yoshida M, Gounni AS, Martin JG, Hamid Q (2009) Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix metalloproteinases and migratory function of human airway smooth muscle cells. Clin Exp Allergy 39(9):1370–1380

    Article  PubMed  CAS  Google Scholar 

  29. James AL, Bai TR, Mauad T, Abramson MJ, Dolhnikoff M, McKay KO, Maxwell PS, Elliot JG, Green FH (2009) Airway smooth muscle thickness in asthma is related to severity but not duration of asthma. Eur Respir J 34(5):1040–1045

    Article  PubMed  CAS  Google Scholar 

  30. James AL, Pare PD, Hogg JC (1989) The mechanics of airway narrowing in asthma. Am Rev Respir Dis 139(1):242–246

    Article  PubMed  CAS  Google Scholar 

  31. Ju H, Scammel-La Fleur T, Dixon IM (1996) Altered mRNA abundance of calcium transport genes in cardiac myocytes induced by angiotensin II. J Mol Cell Cardiol 28(5):1119–1128

    Article  PubMed  CAS  Google Scholar 

  32. Kumar B, Dreja K, Shah SS, Cheong A, Xu SZ, Sukumar P, Naylor J, Forte A, Cipollaro M, McHugh D, Kingston PA, Heagerty AM, Munsch CM, Bergdahl A, Hultgardh-Nilsson A, Gomez MF, Porter KE, Hellstrand P, Beech DJ (2006) Upregulated TRPC1 channel in vascular injury in vivo and its role in human neointimal hyperplasia. Circ Res 98(4):557–563. doi:10.1161/01.RES.0000204724.29685.db

    Article  PubMed  CAS  Google Scholar 

  33. Leigh R, Ellis R, Wattie J, Southam DS, De Hoogh M, Gauldie J, O’Byrne PM, Inman MD (2002) Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced airway inflammation. Am J Respir Cell Mol Biol 27(5):526–535

    PubMed  CAS  Google Scholar 

  34. Leung SY, Eynott P, Noble A, Nath P, Chung KF (2004) Resolution of allergic airways inflammation but persistence of airway smooth muscle proliferation after repeated allergen exposures. Clin Exp Allergy 34(2):213–220

    Article  PubMed  CAS  Google Scholar 

  35. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+ -store-depletion-triggered Ca2+ influx. Curr Biol 15(13):1235–1241

    Article  PubMed  CAS  Google Scholar 

  36. Lipskaia L, del Monte F, Capiod T, Yacoubi S, Hadri L, Hours M, Hajjar RJ, Lompre AM (2005) Sarco/endoplasmic reticulum Ca2+ -ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat. Circ Res 97(5):488–495

    Article  PubMed  CAS  Google Scholar 

  37. Locksley RM (2010) Asthma and allergic inflammation. Cell 140(6):777–783

    Article  PubMed  CAS  Google Scholar 

  38. Mahn K, Hirst SJ, Ying S, Holt MR, Lavender P, Ojo OO, Siew L, Simcock DE, McVicker CG, Kanabar V, Snetkov VA, O’Connor BJ, Karner C, Cousins DJ, Macedo P, Chung KF, Corrigan CJ, Ward JP, Lee TH (2009) Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma. Proc Natl Acad Sci U S A 106(26):10775–10780

    Article  PubMed  CAS  Google Scholar 

  39. Mahn K, Ojo OO, Chadwick G, Aaronson PI, Ward JP, Lee TH (2010) Ca(2+) homeostasis and structural and functional remodelling of airway smooth muscle in asthma. Thorax 65(6):547–552

    Article  PubMed  Google Scholar 

  40. McMillan SJ, Lloyd CM (2004) Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy 34(3):497–507

    Article  PubMed  CAS  Google Scholar 

  41. Motiani RK, Abdullaev IF, Trebak M (2010) A novel native store-operated calcium channel encoded by Orai3: selective requirement of Orai3 versus Orai1 in estrogen receptor-positive versus estrogen receptor-negative breast cancer cells. J Biol Chem 285(25):19173–19183

    Article  PubMed  CAS  Google Scholar 

  42. Muik M, Fahrner M, Derler I, Schindl R, Bergsmann J, Frischauf I, Groschner K, Romanin C (2009) A cytosolic homomerization and a modulatory domain within STIM1 C-terminus determine coupling to ORAI1 channels. J Biol Chem 284:8421–8426

    Article  PubMed  CAS  Google Scholar 

  43. Murphy DM, O’Byrne PM (2010) Recent advances in the pathophysiology of asthma. Chest 137(6):1417–1426

    Article  PubMed  CAS  Google Scholar 

  44. Neylon CB, Lang RJ, Fu Y, Bobik A, Reinhart PH (1999) Molecular cloning and characterization of the intermediate-conductance Ca(2+)-activated K(+) channel in vascular smooth muscle: relationship between K(Ca) channel diversity and smooth muscle cell function. Circ Res 85(9):e33–e43

    Article  PubMed  CAS  Google Scholar 

  45. Ohno I, Nitta Y, Yamauchi K, Hoshi H, Honma M, Woolley K, O’Byrne P, Dolovich J, Jordana M, Tamura G et al (1995) Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF-B) in nasal polyposis and bronchial asthma. Am J Respir Cell Mol Biol 13(6):639–647

    PubMed  CAS  Google Scholar 

  46. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136(5):876–890

    Article  PubMed  CAS  Google Scholar 

  47. Peel SE, Liu B, Hall IP (2006) A key role for STIM1 in store operated calcium channel activation in airway smooth muscle. Respir Res 7:119

    Article  PubMed  Google Scholar 

  48. Peel SE, Liu B, Hall IP (2008) ORAI and store-operated calcium influx in human airway smooth muscle cells. Am J Respir Cell Mol Biol 38(6):744–749

    Article  PubMed  CAS  Google Scholar 

  49. Pepe C, Foley S, Shannon J, Lemiere C, Olivenstein R, Ernst P, Ludwig MS, Martin JG, Hamid Q (2005) Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol 116(3):544–549

    Article  PubMed  Google Scholar 

  50. Perez-Zoghbi JF, Karner C, Ito S, Shepherd M, Alrashdan Y, Sanderson MJ (2009) Ion channel regulation of intracellular calcium and airway smooth muscle function. Pulm Pharmacol Ther 22(5):388–397

    Article  PubMed  CAS  Google Scholar 

  51. Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23(8):2425–2437. doi:10.1096/fj.09-131128

    Article  PubMed  CAS  Google Scholar 

  52. Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7(1):1–12

    Article  PubMed  CAS  Google Scholar 

  53. Putney JW Jr (1990) Capacitative calcium entry revisited. Cell Calcium 11(10):611–624

    Article  PubMed  CAS  Google Scholar 

  54. Putney JW (2009) Capacitative calcium entry: from concept to molecules. Immunol Rev 231(1):10–22

    Article  PubMed  CAS  Google Scholar 

  55. Qi M, Puglisi JL, Byron KL, Ojamaa K, Klein I, Bers DM, Samarel AM (1997) Myosin heavy chain gene expression in neonatal rat heart cells: effects of [Ca2+]i and contractile activity. Am J Physiol 273(2 Pt 1):C394–C403

    PubMed  CAS  Google Scholar 

  56. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169(3):435–445

    Article  PubMed  CAS  Google Scholar 

  57. Shepherd MC, Duffy SM, Harris T, Cruse G, Schuliga M, Brightling CE, Neylon CB, Bradding P, Stewart AG (2007) KCa3.1 Ca2+ activated K + channels regulate human airway smooth muscle proliferation. Am J Respir Cell Mol Biol 37(5):525–531

    Article  PubMed  CAS  Google Scholar 

  58. Shimizu S, Gabazza EC, Hayashi T, Ido M, Adachi Y, Suzuki K (2000) Thrombin stimulates the expression of PDGF in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 279(3):L503–L510

    PubMed  CAS  Google Scholar 

  59. Snetkov VA, Hirst SJ, Twort CH, Ward JP (1995) Potassium currents in human freshly isolated bronchial smooth muscle cells. Br J Pharmacol 115(6):1117–1125

    Article  PubMed  CAS  Google Scholar 

  60. Snetkov VA, Hirst SJ, Ward JP (1996) Ion channels in freshly isolated and cultured human bronchial smooth muscle cells. Exp Physiol 81(5):791–804

    PubMed  CAS  Google Scholar 

  61. Tharp DL, Wamhoff BR, Turk JR, Bowles DK (2006) Upregulation of intermediate-conductance Ca2+ -activated K + channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle. Am J Physiol Heart Circ Physiol 291(5):H2493–H2503

    Article  PubMed  CAS  Google Scholar 

  62. Tillie-Leblond I, de Blic J, Jaubert F, Wallaert B, Scheinmann P, Gosset P (2008) Airway remodeling is correlated with obstruction in children with severe asthma. Allergy 63(5):533–541

    Article  PubMed  CAS  Google Scholar 

  63. Trebak M, Bird GS, McKay RR, Putney JW Jr (2002) Comparison of human TRPC3 channels in receptor-activated and store-operated modes. Differential sensitivity to channel blockers suggests fundamental differences in channel composition. J Biol Chem 277(24):21617–21623. doi:10.1074/jbc.M202549200

    Article  PubMed  CAS  Google Scholar 

  64. Trebak M, Lemonnier L, Dehaven WI, Wedel BJ, Bird GS, Putney JW Jr (2009) Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Arch 457(4):757–769

    Article  PubMed  CAS  Google Scholar 

  65. Trebak M, St JBG, McKay RR, Birnbaumer L, Putney JW Jr (2003) Signaling mechanism for receptor-activated canonical transient receptor potential 3 (TRPC3) channels. J Biol Chem 278(18):16244–16252. doi:10.1074/jbc.M300544200

    Article  PubMed  CAS  Google Scholar 

  66. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science (New York, NY) 312(5777):1220–1223

    Article  CAS  Google Scholar 

  67. Walter MJ, Holtzman MJ (2005) A centennial history of research on asthma pathogenesis. Am J Respir Cell Mol Biol 32(6):483–489

    Article  PubMed  CAS  Google Scholar 

  68. Wu X, Eder P, Chang B, Molkentin JD (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci USA 107(15):7000–7005

    Article  PubMed  CAS  Google Scholar 

  69. Xiao JH, Zheng YM, Liao B, Wang YX (2010) Functional role of TRPC1 and TRPC3 in normal and asthmatic airway smooth muscle. Am J Respir Cell Mol Biol 43:17–25

    Article  PubMed  CAS  Google Scholar 

  70. Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ, Yuan JX (2004) Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101(38):13861–13866. doi:10.1073/pnas.0405908101

    Article  PubMed  CAS  Google Scholar 

  71. Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11(3):337–343

    Article  PubMed  CAS  Google Scholar 

  72. Zhang SL, Yeromin AV, Zhang XH, Yu Y, Safrina O, Penna A, Roos J, Stauderman KA, Cahalan MD (2006) Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity. Proc Natl Acad Sci USA 103(24):9357–9362

    Article  PubMed  CAS  Google Scholar 

  73. Zhang W, Halligan KE, Zhang X, Bisaillon JM, Gonzalez-Cobos JC, Motiani RK, Hu G, Vincent PA, Zhou J, Barroso M, Singer HA, Matrougui K, Trebak M (2011) Orai1-mediated I (CRAC) is essential for neointima formation after vascular injury. Circ Res 109(5):534–542

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was mainly supported by grant HL097111 from NIH to MT and in part by NIH grants R01HL49426 to HAS and HL095566 to KM.

Author information

Authors and Affiliations

  1. Center for Cardiovascular Sciences, Albany Medical College, Mail Code 8, 47 New Scotland Ave, Albany, NY, 12208, USA

    Amy M. Spinelli, José C. González-Cobos, Xuexin Zhang, Rajender K. Motiani, Sarah Rowan, Wei Zhang, Joshua Garrett, Peter A. Vincent, Harold A. Singer & Mohamed Trebak

  2. Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA, 70112, USA

    Khalid Matrougui

Authors
  1. Amy M. Spinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José C. González-Cobos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuexin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajender K. Motiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sarah Rowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joshua Garrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter A. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Khalid Matrougui
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harold A. Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mohamed Trebak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed Trebak.

Additional information

Amy Spinelli, José C. González-Cobos, Xuexin Zhang, and Rajender K. Motiani contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spinelli, A.M., González-Cobos, J.C., Zhang, X. et al. Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflugers Arch - Eur J Physiol 464, 481–492 (2012). https://doi.org/10.1007/s00424-012-1160-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-012-1160-5

Keywords

Search

Navigation