Cross Talk Between Plasma Membrane Na+/Ca2+ Exchanger-1 and TRPC/Orai-Containing Channels: Key Players in Arterial Hypertension

  • Maria V. Pulina
  • A. Zulian
  • Sergey G. Baryshnikov
  • Cristina I. Linde
  • Eiji Karashima
  • John M. Hamlyn
  • Patrizia Ferrari
  • Mordecai P. Blaustein
  • Vera A. GolovinaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 961)


Arterial smooth muscle (ASM) Na+/Ca2+ exchanger type 1 (NCX1) and TRPC/Orai-containing receptor/store-operated cation channels (ROC/SOC) are clustered with α2 Na+ pumps in plasma membrane microdomains adjacent to the underlying junctional sarcoplasmic reticulum. This arrangement enables these transport proteins to function as integrated units to help regulate local Na+ metabolism, Ca2+ signaling, and arterial tone. They thus influence vascular resistance and blood pressure (BP). For instance, upregulation of NCX1 and TRPC6 has been implicated in the pathogenesis of high BP in several models of essential hypertension. The models include ouabain-induced hypertensive rats, Milan hypertensive rats, and Dahl salt-sensitive hypertensive rats, all of which exhibit elevated plasma ouabain levels. We suggest that these molecular mechanisms are key contributors to the increased vascular resistance (“whole body autoregulation”) that elevates BP in essential hypertension. Enhanced expression and function of ASM NCX1 and TRPC/Orai1-containing channels in hypertension implies that these proteins are potential targets for pharmacological intervention.


Arterial smooth muscle cells Ca2+ signaling Store-operated channels Receptor-operated channels TRPC6 Ouabain-induced hypertensive rats Milan hypertensive strain rats Dahl salt-sensitive hypertensive rats 


  1. A. Arnon, J.M. Hamlyn, M.P. Blaustein, Na+ entry via store-operated channels modulates Ca2+ signaling in arterial myocytes. Am. J. Physiol. Cell Physiol. 278, C163–C173 (2000)PubMedGoogle Scholar
  2. Y.M. Bae, A. Kim, Y.J. Lee, W. Lim, Y.H. Noh, E.J. Kim, J. Kim, T.K. Kim, S.W. Park, B. Kim, S.I. Cho, D.K. Kim, W.K. Ho, Enhancement of receptor-operated cation current and TRPC6 expression in arterial smooth muscle cells of deoxycorticosterone acetate-salt hypertensive rats. J. Hypertens. 25, 809–817 (2007)PubMedCrossRefGoogle Scholar
  3. S.G. Baryshnikov, M.V. Pulina, A. Zulian, C.I. Linde, V.A. Golovina, Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger in proliferating human arterial myocytes. Am. J. Physiol. Cell Physiol. 297, C1103–C1112 (2009)PubMedCrossRefGoogle Scholar
  4. D.J. Beech, K. Muraki, R. Flemming, Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP. J. Physiol. 559, 685–706 (2004)PubMedCrossRefGoogle Scholar
  5. M.P. Blaustein, J.M. Hamlyn, Signaling mechanisms that link salt retention to hypertension: endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins. Biochim. Biophys. Acta 1802, 1219–1229 (2010)PubMedCrossRefGoogle Scholar
  6. M.P. Blaustein, W.J. Lederer, Sodium/calcium exchange: its physiological implications. Physiol. Rev. 79, 763–854 (1999)PubMedGoogle Scholar
  7. M.P. Blaustein, J. Zhang, L. Chen, H. Song, H. Raina, S.P. Kinsey, M. Izuka, T. Iwamoto, M.I. Kotlikoff, J.B. Lingrel, K.D. Philipson, W.G. Wier, J.M. Hamlyn, The pump, the exchanger, and endogenous ouabain: signaling mechanisms that link salt retention to hypertension. Hypertension 53, 291–298 (2009)PubMedCrossRefGoogle Scholar
  8. B.R. Boulanger, M.P. Lilly, J.M. Hamlyn, J. Laredo, D. Shurtleff, D.S. Gann, Ouabain is secreted by the adrenal gland in awake dogs. Am. J. Physiol. 264, E413–E419 (1993)PubMedGoogle Scholar
  9. J.E. Brayden, S. Earley, M.T. Nelson, S. Reading, Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow. Clin. Exp. Pharmacol. Physiol. 35, 1116–1120 (2008)PubMedCrossRefGoogle Scholar
  10. M.D. Cahalan, STIMulating store-operated Ca2+ entry. Nat. Cell Biol. 11, 69–77 (2009)CrossRefGoogle Scholar
  11. X. Chen, D. Yang, S. Ma, H. He, Z. Luo, X. Feng, T. Cao, L. Ma, Z. Yan, D. Liu, M. Tepel, Z. Zhu, Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels. J. Cell. Mol. Med. 14, 2483–2494 (2010)PubMedCrossRefGoogle Scholar
  12. A.W. Cowley Jr., Long-term control of arterial blood pressure. Physiol. Rev. 72, 231–300 (1992)PubMedGoogle Scholar
  13. M.J. Davis, M.A. Hill, Signaling mechanisms underlying the vascular myogenic response. Physiol. Rev. 79, 387–423 (1999)PubMedGoogle Scholar
  14. K.M. Dibb, H.K. Graham, L.A. Venetucci, D.A. Eisner, A.W. Trafford, Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart. Cell Calcium 42, 503–512 (2007)PubMedCrossRefGoogle Scholar
  15. I. Dostanic-Larson, J.W. Van Huysse, J.N. Lorenz, J.B. Lingrel, The highly conserved cardiac glycoside binding site of Na+, K  +  - ATPase plays a role in blood pressure regulation. Proc. Natl. Acad. Sci. U. S. A. 102, 15845–15850 (2005)PubMedCrossRefGoogle Scholar
  16. P. Eder, M. Poteser, C. Romanin, K. Groschner, Na+ entry and modulation of Na+/Ca2+ exchange as a key mechanism of TRPC signaling. Pflugers Arch. 451, 99–104 (2005)PubMedCrossRefGoogle Scholar
  17. S.K. Fellner, W.J. Arendshorst, Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange. Am. J. Physiol. Renal Physiol. 294, F212–F219 (2008)PubMedCrossRefGoogle Scholar
  18. M. Ferrandi, G. Tripodi, S. Salardi, M. Florio, R. Modica, P. Barassi, P. Parenti, A. Shainskaya, S. Karlish, G. Bianchi, P. Ferrari, Renal Na+, K  +  -ATPase in genetic hypertension. Hypertension 28, 1018–1025 (1996)PubMedCrossRefGoogle Scholar
  19. M. Ferrandi, P. Manunta, S. Balzan, J.M. Hamlyn, G. Bianchi, P. Ferrari, Ouabain-like factor quantification in mammalian tissues and plasma: comparison of two independent assays. Hypertension 30, 886–896 (1997)PubMedCrossRefGoogle Scholar
  20. M. Ferrandi, S. Salardi, G. Tripodi, P. Barassi, R. Rivera, P. Manunta, R. Goldshleger, P. Ferrari, G. Bianchi, S.J. Karlish, Evidence for an interaction between adducin and Na+-K+-ATPase: relation to genetic hypertension. Am. J. Physiol. 277, H1338–H1349 (1999)PubMedGoogle Scholar
  21. R. Flemming, A. Cheong, A.M. Dedman, D.J. Beech, Discrete store-operated calcium influx into an intracellular compartment in rabbit arteriolar smooth muscle. J. Physiol. 543, 455–464 (2002)PubMedCrossRefGoogle Scholar
  22. F.R. Giachini, C.W. Chiao, F.S. Carneiro, V.V. Lima, Z.N. Carneiro, A.M. Dorrance, R.C. Tostes, R.C. Webb, Increased activation of stromal interaction molecule-1/Orai-1 in aorta from hypertensive rats: a novel insight into vascular dysfunction. Hypertension 53, 409–416 (2009)PubMedCrossRefGoogle Scholar
  23. V.A. Golovina, Visualization of localized store-operated calcium entry in mouse astrocytes. Close proximity to the endoplasmic reticulum. J. Physiol. 564, 737–749 (2005)PubMedCrossRefGoogle Scholar
  24. J.M. Hamlyn, M.P. Blaustein, S. Bova, D.W. DuCharme, D.W. Harris, F. Mandel, W.R. Mathews, J.H. Ludens, Identification and characterization of a ouabain-like compound from human plasma. Proc. Natl. Acad. Sci. U. S. A. 88, 6259–6263 (1991)PubMedCrossRefGoogle Scholar
  25. T. Iwamoto, S. Kita, J. Zhang, M.P. Blaustein, Y. Arai, S. Yoshida, K. Wakimoto, I. Komuro, T. Katsuragi, Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger type-1 in vascular smooth muscle. Nat. Med. 10, 1193–1199 (2004)PubMedCrossRefGoogle Scholar
  26. M. Juhaszova, M.P. Blaustein, Na+ pump low and high ouabain affinity alpha subunit isoforms are differently distributed in cells. Proc. Natl. Acad. Sci. U. S. A. 94, 1800–1805 (1997)PubMedCrossRefGoogle Scholar
  27. M. Juhaszova, H. Shimizu, M.L. Borin, R.K. Yip, E.M. Santiago, G.E. Lindenmayer, M.P. Blaustein, Localization of the Na+/Ca2+ exchanger in vascular smooth muscle, and in neurons and astrocytes. Ann. N. Y. Acad. Sci. 779, 318–335 (1996)PubMedCrossRefGoogle Scholar
  28. J. Kaide, N. Ura, T. Torii, M. Nakagawa, T. Takada, K. Shimamoto, Effects of digoxin-specific antibody Fab fragment (Digibind) on blood pressure and renal water-sodium metabolism in 5/6 reduced renal mass hypertensive rats. Am. J. Hypertens. 12, 611–619 (1999)PubMedCrossRefGoogle Scholar
  29. T. Kashihara, K. Nakayama, T. Matsuda, A. Baba, T. Ishikawa, Role of Na+/Ca2+ exchanger-mediated Ca2+ entry in pressure-induced myogenic constriction in rat posterior cerebral arteries. J. Pharmacol. Sci. 110, 218–222 (2009)PubMedCrossRefGoogle Scholar
  30. H. Krep, D.A. Price, P. Soszynski, Q.F. Tao, S.W. Graves, N.K. Hollenberg, Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats. Am. J. Hypertens. 8, 921–927 (1995)PubMedCrossRefGoogle Scholar
  31. G.J. Lagaud, V. Randriamboavonjy, G. Roulm, J.C. Stoclet, R. Andriantsitohaina, Mechanism of Ca2+ release and entry during contraction elicited by norepinephrine in rat resistance arteries. Am. J. Physiol. 276, H300–H308 (1999)PubMedGoogle Scholar
  32. M.Y. Lee, H. Song, J. Nakai, M. Ohkura, M.I. Kotlikoff, S.P. Kinsey, V.A. Golovina, M.P. Blaustein, Local subplasma membrane Ca2+ signals detected by a tethered Ca2+ sensor. Proc. Natl. Acad. Sci. U. S. A. 103, 13232–13237 (2006)PubMedCrossRefGoogle Scholar
  33. F.H. Leenen, E. Harmsen, H. Yu, Dietary sodium and central vs peripheral ouabain-like activity in Dahl salt-sensitive vs salt-resistant rats. Am. J. Physiol. 267, H1916–H1920 (1994)PubMedGoogle Scholar
  34. J. Li, P. Sukumar, C.J. Milligan, B. Kumar, Z.Y. Ma, C.M. Munsch, L.H. Jiang, K.E. Porter, D.J. Beech, Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in vascular smooth muscle cells. Circ. Res. 103, e97–e104 (2008)PubMedCrossRefGoogle Scholar
  35. Y. Liao, C. Erxleben, J. Abramowitz, V. Flockerzi, M.X. Zhu, D.L. Armstrong, L. Birnbaumer, Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc. Natl. Acad. Sci. U. S. A. 105, 2895–2900 (2008)PubMedCrossRefGoogle Scholar
  36. D. Liu, D. Yang, H. He, X. Chen, T. Cao, X. Feng, L. Ma, Z. Luo, L. Wang, Z. Yan, Z. Zhu, M. Tepel, Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats. Hypertension 53, 70–76 (2009)PubMedCrossRefGoogle Scholar
  37. J.N. Lorenz, E.L. Loreaux, I. Dostanic-Larson, V. Lasko, J.R. Schnetzer, R.J. Paul, J.B. Lingrel, ACTH-induced hypertension is dependent on the ouabain-binding site of the alpha2-Na+, K  +  -ATPase subunit. Am. J. Physiol. Heart Circ. Physiol. 295, H273–H280 (2008)PubMedCrossRefGoogle Scholar
  38. P. Manunta, A.C. Rogowski, B.P. Hamilton, J.M. Hamlyn, Ouabain-induced hypertension in the rat: relationships among plasma and tissue ouabain and blood pressure. J. Hypertens. 12, 549–560 (1994)PubMedCrossRefGoogle Scholar
  39. S.S. McDaniel, O. Platoshyn, J. Wang, Y. Yu, M. Sweeney, S. Krick, L.J. Rubin, J.X. Yuan, Capacitative Ca2+ entry in agonist- induced pulmonary vasoconstriction. Am. J. Physiol. Lung Cell. Mol. Physiol. 280, L870–L880 (2001)PubMedGoogle Scholar
  40. M.T. Nelson, J.B. Patlak, J.F. Worley, N.B. Standen, Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am. J. Physiol. 259, C3–C18 (1990)PubMedGoogle Scholar
  41. L.C. Ng, D. Ramduny, J.A. Airey, C.A. Singer, P.S. Keller, X.M. Shen, H. Tian, M. Valencik, J.R. Hume, Orai1 interacts with STIM1 and mediates capacitative Ca2+ entry in mouse pulmonary arterial smooth muscle cells. Am. J. Physiol. Cell Physiol. 299, C1079–C1090 (2010)PubMedCrossRefGoogle Scholar
  42. B. Nilius, G. Owsianik, T. Voets, J.A. Peters, Transient receptor potential cation channels in disease. Physiol. Rev. 87, 165–217 (2007)PubMedCrossRefGoogle Scholar
  43. W.J. O’Brien, J.B. Lingrel, E.T. Wallick, Ouabain binding kinetics of the rat alpha two and alpha three isoforms of the sodium-potassium adenosine triphosphate. Arch. Biochem. Biophys. 310, 32–39 (1994)PubMedCrossRefGoogle Scholar
  44. D. Poburko, K. Potter, E. van Breemen, N. Fameli, C.H. Liao, O. Basset, U.T. Ruegg, C. van Breemen, Mitochondria buffer NCX-mediated Ca2+-entry and limit its diffusion into vascular smooth muscle cells. Cell Calcium 40, 359–371 (2006)PubMedCrossRefGoogle Scholar
  45. D. Poburko, C.H. Liao, V.S. Lemos, E. Lin, Y. Maruyama, W.C. Cole, C. van Breemen, Transient receptor potential channel 6- mediated, localized cytosolic [Na+] transients drive Na+/Ca2+ exchanger-mediated Ca2+ entry in purinergically stimulated aorta smooth muscle cells. Circ. Res. 101, 1030–1038 (2007)PubMedCrossRefGoogle Scholar
  46. M. Potier, J.C. Gonzalez, R.K. Motiani, I.F. Abdullaev, J.M. Bisaillon, H.A. Singer, M. Trebak, 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, 2425–2437 (2009)PubMedCrossRefGoogle Scholar
  47. M.V. Pulina, A. Zulian, R. Berra-Romani, O. Beskina, A. Mazzocco-Spezzia, S.G. Baryshnikov, I. Papparella, J.M. Hamlyn, M.P. Blaustein, V.A. Golovina, Up-regulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 298, H263–H274 (2010)PubMedCrossRefGoogle Scholar
  48. C. Rosker, A. Graziani, M. Lukas, P. Eder, M.X. Zhu, C. Romanin, K. Groschner, Ca2+ signaling by TRPC3 involves Na+ entry and local coupling to the Na+/Ca2+ exchanger. J. Biol. Chem. 279, 13696–13704 (2004)PubMedCrossRefGoogle Scholar
  49. G. Rossi, P. Manunta, J.M. Hamlyn, E. Pavan, R. De Toni, A. Semplicini, A.C. Pessina, Immunoreactive endogenous ouabain in primary aldosteronism and essential hypertension: relationship with plasma renin, aldosterone and blood pressure levels. J. Hypertens. 13, 1181–1191 (1995)PubMedCrossRefGoogle Scholar
  50. K.M. Sanders, Invited review: mechanisms of calcium handling in smooth muscles. J. Appl. Physiol. 91, 1438–1449 (2001)PubMedGoogle Scholar
  51. J.R. Shah, J. Laredo, B.P. Hamilton, J.M. Hamlyn, Different signaling pathways mediate stimulated secretions of endogenous ouabain and aldosterone from bovine adrenocortical cells. Hypertension 31, 463–468 (1998)PubMedCrossRefGoogle Scholar
  52. D.A. Shelly, S. He, A. Moseley, C. Weber, M. Stegemeyer, R.M. Lynch, J. Lingrel, R.J. Paul, Na+ pump alpha 2-isoform specifically couples to contractility in vascular smooth muscle: evidence from gene-targeted neonatal mice. Am. J. Physiol. Cell Physiol. 286, C813–C820 (2004)PubMedCrossRefGoogle Scholar
  53. A.V. Somlyo, C. Franzini-Armstrong, New views of smooth muscle structure using freezing, deep-etching and rotary shadowing. Experientia 41, 841–856 (1985)PubMedCrossRefGoogle Scholar
  54. H. Song, M.Y. Lee, S.P. Kinsey, D.J. Weber, M.P. Blaustein, An N-terminal sequence targets and tethers Na+ pump alpha2 subunits to specialized plasma membrane microdomains. J. Biol. Chem. 281, 12929–12940 (2006)PubMedCrossRefGoogle Scholar
  55. S. Taniguchi, K. Furukawa, S. Sasamura, Y. Ohizumi, K. Seya, S. Motomura, Gene expression and functional activity of sodium/calcium exchanger enhanced in vascular smooth muscle cells of spontaneously hypertensive rats. J. Cardiovasc. Pharmacol. 43, 629–637 (2004)PubMedCrossRefGoogle Scholar
  56. C. van Breemen, Q. Chen, I. Laher, Superficial buffer barrier function of smooth muscle sarcoplasmic reticulum. Trends Pharmacol. Sci. 16, 98–105 (1995)PubMedCrossRefGoogle Scholar
  57. D.G. Welsh, A.D. Morielli, M.T. Nelson, J.E. Brayden, Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ. Res. 90, 248–250 (2002)PubMedCrossRefGoogle Scholar
  58. M.M. Wu, J. Buchanan, R.M. Luik, R.S. Lewis, Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J. Cell Biol. 174, 803–813 (2006)PubMedCrossRefGoogle Scholar
  59. A.V. Yeromin, S.L. Zhang, W. Jiang, Y. Yu, O. Safrina, M.D. Cahalan, Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443, 226–229 (2006)PubMedCrossRefGoogle Scholar
  60. Y. Yu, I. Fantozzi, C.V. Remillard, J.W. Landsberg, N. Kunichika, O. Platoshyn, D.D. Tigno, P.A. Thistlethwaite, L.J. Rubin, J.X. Yuan, Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc. Natl. Acad. Sci. U. S. A. 101, 13861–13866 (2004)PubMedCrossRefGoogle Scholar
  61. Y. Yu, S.H. Keller, C.V. Remillard, O. Safrina, A. Nicholson, S.L. Zhang, W. Jiang, N. Vangala, J.W. Landsberg, J.Y. Wang, P.A. Thistlethwaite, R.N. Channick, I.M. Robbins, J.E. Loyd, H.A. Ghofrani, F. Grimminger, R.T. Schermuly, M.D. Cahalan, L.J. Rubin, J.X. Yuan, A functional single-nucleotide ­polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119, 2313–2322 (2009)PubMedCrossRefGoogle Scholar
  62. J.P. Yuan, M.S. Kim, W. Zeng, D.M. Shin, G. Huang, P.F. Worley, S. Muallem, TRPC channels as STIM1-regulated SOCs. Channels (Austin) 3, 221–225 (2009)CrossRefGoogle Scholar
  63. J. Zhang, M.Y. Lee, M. Cavalli, L. Chen, R. Berra-Romani, C.W. Balke, G. Bianchi, P. Ferrari, J.M. Hamlyn, T. Iwamoto, J.B. Lingrel, D.R. Matteson, W.G. Wier, M.P. Blaustein, Sodium pump alpha2 subunits control myogenic tone and blood pressure in mice. J. Physiol. 569, 243–256 (2005a)PubMedCrossRefGoogle Scholar
  64. S.L. Zhang, Y. Yu, J. Roos, J.A. Kozak, T.J. Deerinck, M.H. Ellisman, K.A. Stauderman, M.D. Cahalan, STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437, 902–905 (2005b)PubMedCrossRefGoogle Scholar
  65. S. Zhang, H. Dong, L.J. Rubin, J.X. 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. 292, C2297–C2305 (2007a)PubMedCrossRefGoogle Scholar
  66. S. Zhang, H.H. Patel, F. Murray, C.V. Remillard, C. Schach, P.A. Thistlethwaite, P.A. Insel, J.X. Yuan, Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry. Am. J. Physiol. Lung Cell. Mol. Physiol. 292, L1202–L1210 (2007b)PubMedCrossRefGoogle Scholar
  67. J. Zhang, C. Ren, L. Chen, M.F. Navedo, L.K. Antos, S.P. Kinsey, T. Iwamoto, K.D. Philipson, M.I. Kotlikoff, L.F. Santana, W.G. Wier, D.R. Matteson, M.P. Blaustein, Knockout of Na+/Ca2+ exchanger in smooth muscle attenuates vasoconstriction and L-type Ca2+ channel current and lowers blood pressure. Am. J. Physiol. Heart Circ. Physiol. 298, H1472–H1483 (2010)PubMedCrossRefGoogle Scholar
  68. H. Zou, P.H. Ratz, M.A. Hill, Temporal aspects of Ca2+ and myosin phosphorylation during myogenic and norepinephrine-induced arteriolar constriction. J. Vasc. Res. 37, 556–567 (2000)PubMedCrossRefGoogle Scholar
  69. A. Zulian, S.G. Baryshnikov, C.I. Linde, J.M. Hamlyn, P. Ferrari, V.A. Golovina, Upregulation of Na+/Ca2+ exchanger and TRPC6 contributes to abnormal Ca2+ homeostasis in arterial smooth muscle cells from Milan hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 299, H624–H633 (2010)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Maria V. Pulina
    • 1
  • A. Zulian
    • 1
  • Sergey G. Baryshnikov
    • 1
  • Cristina I. Linde
    • 1
  • Eiji Karashima
    • 1
  • John M. Hamlyn
    • 1
  • Patrizia Ferrari
    • 2
  • Mordecai P. Blaustein
    • 1
  • Vera A. Golovina
    • 1
    Email author
  1. 1.Department of PhysiologyUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Prassis-sigma tau Research InstituteMilanItaly

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