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Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle

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Abstract

Recent studies suggest that primary changes in vascular resistance can cause sustained changes in arterial blood pressure. In this review, we summarize current knowledge about Cl− homeostasis in vascular smooth muscle cells. Within vascular smooth muscle cells, Cl− is accumulated above the electrochemical equilibrium, causing Cl− efflux, membrane depolarization, and increased contractile force when Cl− channels are opened. At least two different transport mechanisms contribute to raise [Cl−] i in vascular smooth muscle cells, anion exchange, and cation-chloride cotransport. Recent work suggests that TMEM16A-associated Ca2+-activated Cl− currents mediate Cl− efflux in vascular smooth muscle cells leading to vasoconstriction. Additional proteins associated with Cl− flux in vascular smooth muscle are bestrophins, which modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl− transporters and Cl− channels in vascular smooth muscle cells (VSMCs) significantly contribute to the physiological regulation of vascular tone and arterial blood pressure.

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References

  1. Adragna NC, White RE, Orlov SN, Lauf PK (2000) K-Cl cotransport in vascular smooth muscle and erythrocytes: possible implication in vasodilation. Am J Physiol Cell Physiol 278:C381–C390

    CAS  PubMed  Google Scholar 

  2. Aickin CC, Vermue NA (1983) Microelectrode measurement of intracellular chloride activity in smooth muscle cells of guinea-pig ureter. Pflugers Arch 397:25–28

    CAS  PubMed  Google Scholar 

  3. Aickin CC, Brading AF (1982) Measurement of intracellular chloride in guinea-pig vas deferens by ion analysis, 36chloride efflux and micro-electrodes. J Physiol 326:139–154

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Alvarez BV, Gilmour GS, Mema SC, Martin BT, Shull GE, Casey JR, Sauve Y (2007) Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. PLoS One 2:e839

    PubMed Central  PubMed  Google Scholar 

  5. Anfinogenova YJ, Baskakov MB, Kovalev IV, Kilin AA, Dulin NO, Orlov SN (2004) Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl- cotransport, intracellular Cl- and L-type Ca2+ channels. Pflugers Arch 449:42–55

    CAS  PubMed  Google Scholar 

  6. Bader CR, Bertrand D, Schwartz EA (1982) Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina. J Physiol 331:253–284

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Barish ME (1983) A transient calcium-dependent chloride current in the immature Xenopus oocyte. J Physiol 342:309–325

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Barro-Soria R, Aldehni F, Almaca J, Witzgall R, Schreiber R, Kunzelmann K (2010) ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel. Pflugers Arch 459:485–497

    CAS  PubMed  Google Scholar 

  9. Bharill S, Fu Z, Palty R, Isacoff EY (2014) Stoichiometry and specific assembly of best ion channels. Proc Natl Acad Sci U S A 111:6491–6496

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Bianchi G, Ferrari P, Trizio D, Ferrandi M, Torielli L, Barber BR, Polli E (1985) Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link. Hypertension 7:319–325

    CAS  PubMed  Google Scholar 

  11. Boettger T, Rust MB, Maier H, Seidenbecher T, Schweizer M, Keating DJ, Faulhaber J, Ehmke H, Pfeffer C, Scheel O, Lemcke B, Horst J, Leuwer R, Pape HC, Volkl H, Hübner CA, Jentsch TJ (2003) Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J 22:5422–5434

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Broegger T, Jacobsen JC, Secher Dam V, Boedtkjer DM, Kold-Petersen H, Pedersen FS, Aalkjaer C, Matchkov VV (2011) Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries. Cardiovasc Res 91:685–693

    CAS  PubMed  Google Scholar 

  13. Brosius FC 3rd, Pisoni RL, Cao X, Deshmukh G, Yannoukakos D, Stuart-Tilley AK, Haller C, Alper SL (1997) AE anion exchanger mRNA and protein expression in vascular smooth muscle cells, aorta, and renal microvessels. Am J Physiol 273:F1039–F1047

    CAS  PubMed  Google Scholar 

  14. Bulley S, Neeb ZP, Burris SK, Bannister JP, Thomas-Gatewood CM, Jangsangthong W, Jaggar JH (2012) TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. Circ Res 111:1027–1036

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Byrne NG, Large WA (1987) The action of noradrenaline on single smooth muscle cells freshly dispersed from the guinea-pig pulmonary artery. Br J Pharmacol 91:89–94

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Byrne NG, Large WA (1988) Membrane ionic mechanisms activated by noradrenaline in cells isolated from the rabbit portal vein. J Physiol 404:557–573

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594

    CAS  PubMed  Google Scholar 

  18. Casteels R, Kitamura K, Kuriyama H, Suzuki H (1977) The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery. J Physiol 271:41–61

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Castrop H, Lorenz JN, Hansen PB, Friis U, Mizel D, Oppermann M, Jensen BL, Briggs J, Skott O, Schnermann J (2005) Contribution of the basolateral isoform of the Na-K-2Cl- cotransporter (NKCC1/BSC2) to renin secretion. Am J Physiol Renal Physiol 289:F1185–F1192

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Chipperfield AR, Harper AA (2000) Chloride in smooth muscle. Prog Biophys Mol Biol 74:175–221

    CAS  PubMed  Google Scholar 

  21. Cho HM, Lee HA, Kim HY, Han HS, Kim IK (2011) Expression of Na+-K+-2Cl- cotransporter 1 is epigenetically regulated during postnatal development of hypertension. Am J Hypertens 24:1286–1293

    CAS  PubMed  Google Scholar 

  22. Coffman TM (2014) The inextricable role of the kidney in hypertension. J Clin Invest 124:2341–2347

    PubMed Central  PubMed  Google Scholar 

  23. Cowley AW, Roman RJ (1996) The role of the kidney in hypertension. JAMA 275:1581–1589

    PubMed  Google Scholar 

  24. Dam VS, Boedtkjer DM, Aalkjaer C, Matchkov V (2014) The bestrophin- and TMEM16A-associated Ca2+- activated Cl- channels in vascular smooth muscles. Channels (Austin) 8:361–369

    Google Scholar 

  25. Dam VS, Boedtkjer DM, Nyvad J, Aalkjaer C, Matchkov V (2014) TMEM16A knockdown abrogates two different Ca2+-activated Cl- currents and contractility of smooth muscle in rat mesenteric small arteries. Pflugers Arch 466:1391–1409

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Davis JP (1992) The effects of Na+-K+-Cl- co-transport and Cl–HCO3-exchange blockade on the membrane potential and intracellular chloride levels of rat arterial smooth muscle, in vitro. Exp Physiol 77:857–862

    CAS  PubMed  Google Scholar 

  27. Davis AJ, Forrest AS, Jepps TA, Valencik ML, Wiwchar M, Singer CA, Sones WR, Greenwood IA, Leblanc N (2010) Expression profile and protein translation of TMEM16A in murine smooth muscle. Am J Physiol Cell Physiol 299:C948–C959

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Davis AJ, Shi J, Pritchard HA, Chadha PS, Leblanc N, Vasilikostas G, Yao Z, Verkman AS, Albert AP, Greenwood IA (2013) Potent vasorelaxant activity of the TMEM16A inhibitor T16Ainh-A01. Br J Pharmacol 168:773–784

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Davis JP, Chien PF, Chipperfield AR, Gordon A, Harper AA (2000) The three mechanisms of intracellular chloride accumulation in vascular smooth muscle of human umbilical and placental arteries. Pflugers Arch 441:150–154

    CAS  PubMed  Google Scholar 

  30. Davis JP, Chipperfield AR, Harper AA (1993) Accumulation of intracellular chloride by (Na-K-Cl) co-transport in rat arterial smooth muscle is enhanced in deoxycorticosterone acetate (DOCA)/salt hypertension. J Mol Cell Cardiol 25:233–237

    CAS  PubMed  Google Scholar 

  31. Doughty JM, Langton PD (2001) Measurement of chloride flux associated with the myogenic response in rat cerebral arteries. J Physiol 534:753–761

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Duan DD (2011) The ClC-3 chloride channels in cardiovascular disease. Acta Pharmacol Sin 32:675–684

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Duran C, Thompson CH, Xiao Q, Hartzell HC (2010) Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 72:95–121

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Forrest AS, Joyce TC, Huebner ML, Ayon RJ, Wiwchar M, Joyce J, Freitas N, Davis AJ, Ye L, Duan DD, Singer CA, Valencik ML, Greenwood IA, Leblanc N (2012) Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension. Am J Physiol Cell Physiol 303:C1229–C1243

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Galmiche G, Pizard A, Gueret A, El Moghrabi S, Ouvrard-Pascaud A, Berger S, Challande P, Jaffe IZ, Labat C, Lacolley P, Jaisser F (2014) Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt to induce vascular stiffness. Hypertension 63:520–526

    CAS  PubMed  Google Scholar 

  36. Gamba G (2005) Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev 85:423–493

    CAS  PubMed  Google Scholar 

  37. Garg P, Martin CF, Elms SC, Gordon FJ, Wall SM, Garland CJ, Sutliff RL, O’Neill WC (2007) Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol 292:H2100–H2105

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Gawenis LR, Ledoussal C, Judd LM, Prasad V, Alper SL, Stuart-Tilley A, Woo AL, Grisham C, Sanford LP, Doetschman T, Miller ML, Shull GE (2004) Mice with a targeted disruption of the AE2 Cl-/HCO3 - exchanger are achlorhydric. J Biol Chem 279:30531–30539

    CAS  PubMed  Google Scholar 

  39. Gerstheimer FP, Mühleisen M, Nehring D, Kreye VA (1987) A chloride-bicarbonate exchanging anion carrier in vascular smooth muscle of the rabbit. Pflugers Arch 409:60–66

    CAS  PubMed  Google Scholar 

  40. Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, Van de Rijn M, West RB, Sarr MG, Kendrick ML, Cima RR, Dozois EJ, Larson DW, Ordog T, Farrugia G (2009) Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 296:G1370–G1381

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Greenwood IA, Leblanc N (2007) Overlapping pharmacology of Ca2+-activated Cl- and K+ channels. Trends Pharmacol Sci 28:1–5

    CAS  PubMed  Google Scholar 

  42. Guo JJ, Stoltz DA, Zhu V, Volk KA, Segar JL, McCray PB Jr, Roghair RD (2014) Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets. J Cyst Fibros 13:251–259

    CAS  PubMed  Google Scholar 

  43. Guyton AC (1991) Blood pressure control—special role of the kidneys and body fluids. Science 252:1813–1816

    CAS  PubMed  Google Scholar 

  44. Guyton AC, Coleman TG, Cowley AV Jr, Scheel KW, Manning RD Jr, Norman RA Jr (1972) Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 52:584–594

    CAS  PubMed  Google Scholar 

  45. Heinze C, Seniuk A, Sokolov MV, Huebner AK, Klementowicz AE, Szijarto IA, Schleifenbaum J, Vitzthum H, Gollasch M, Ehmke H, Schroeder BC, Hübner CA (2014) Disruption of vascular Ca2+-activated chloride currents lowers blood pressure. J Clin Invest 124:675–686

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Hentschke M, Wiemann M, Hentschke S, Kurth I, Hermans-Borgmeyer I, Seidenbecher T, Jentsch TJ, Gal A, Hübner CA (2006) Mice with a targeted disruption of the Cl-/HCO3 - exchanger AE3 display a reduced seizure threshold. Mol Cell Biol 26:182–191

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Hübner CA, Lorke DE, Hermans-Borgmeyer I (2001) Expression of the Na-K-2Cl-cotransporter NKCC1 during mouse development. Mech Dev 102:267–269

    PubMed  Google Scholar 

  48. Hwang SJ, Blair PJ, Britton FC, O’Driscoll KE, Hennig G, Bayguinov YR, Rock JR, Harfe BD, Sanders KM, Ward SM (2009) Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol 587:4887–4904

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Kaplan MR, Plotkin MD, Brown D, Hebert SC, Delpire E (1996) Expression of the mouse Na-K-2Cl cotransporter, mBSC2, in the terminal inner medullary collecting duct, the glomerular and extraglomerular mesangium, and the glomerular afferent arteriole. J Clin Invest 98:723–730

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Kim SM, Eisner C, Faulhaber-Walter R, Mizel D, Wall SM, Briggs JP, Schnermann J (2008) Salt sensitivity of blood pressure in NKCC1-deficient mice. Am J Physiol Renal Physiol 295:F1230–F1238

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Knot HJ, Nelson MT (1998) Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol 508:199–209

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Koltsova SV, Luneva OG, Lavoie JL, Tremblay J, Maksimov GV, Hamet P, Orlov SN (2009) HCO3-dependent impact of Na+, K+, 2Cl- cotransport in vascular smooth muscle excitation-contraction coupling. Cell Physiol Biochem 23:407–414

    CAS  PubMed  Google Scholar 

  53. Koncz C, Daugirdas JT (1994) Use of MQAE for measurement of intracellular [Cl-] in cultured aortic smooth muscle cells. Am J Physiol 267:H2114–H2123

    CAS  PubMed  Google Scholar 

  54. Korbmacher C, Helbig H, Stahl F, Wiederholt M (1988) Evidence for Na/H exchange and Cl/HCO3 exchange in A10 vascular smooth muscle cells. Pflugers Arch 412:29–36

    CAS  PubMed  Google Scholar 

  55. Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (1999) Expression of CLCN voltage-gated chloride channel genes in human blood vessels. J Mol Cell Cardiol 31:657–666

    CAS  PubMed  Google Scholar 

  56. Lamb FS, Kooy NW, Lewis SJ (2000) Role of Cl- channels in alpha-adrenoceptor-mediated vasoconstriction in the anesthetized rat. Eur J Pharmacol 401:403–412

    CAS  PubMed  Google Scholar 

  57. Large WA, Wang Q (1996) Characteristics and physiological role of the Ca2+-activated Cl- conductance in smooth muscle. Am J Physiol 271:C435–C454

    CAS  PubMed  Google Scholar 

  58. Lawes CM, Vander Hoorn S, Rodgers A (2008) Global burden of blood-pressure-related disease, 2001. Lancet 371:1513–1518

    PubMed  Google Scholar 

  59. Liang W, Ray JB, He JZ, Backx PH, Ward ME (2009) Regulation of proliferation and membrane potential by chloride currents in rat pulmonary artery smooth muscle cells. Hypertension 54:286–293

    CAS  PubMed  Google Scholar 

  60. Lieberman J, Rodbard S (1975) Low blood pressure in young adults with cystic fibrosis: an effect of chronic salt loss in sweat? Ann Intern Med 82:806–808

    CAS  PubMed  Google Scholar 

  61. Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104:545–556

    CAS  PubMed  Google Scholar 

  62. Manoury B, Tamuleviciute A, Tammaro P (2010) TMEM16A/anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells. J Physiol 588:2305–2314

    PubMed Central  CAS  PubMed  Google Scholar 

  63. Matchkov VV, Aalkjaer C, Nilsson H (2005) Distribution of cGMP-dependent and cGMP-independent Ca2+-activated Cl- conductances in smooth muscle cells from different vascular beds and colon. Pflugers Arch 451:371–379

    CAS  PubMed  Google Scholar 

  64. Matchkov VV, Larsen P, Bouzinova EV, Rojek A, Boedtkjer DM, Golubinskaya V, Pedersen FS, Aalkjaer C, Nilsson H (2008) Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells. Circ Res 103:864–872

    CAS  PubMed  Google Scholar 

  65. Mattson DL, Lu S, Nakanishi K, Papanek PE, Cowley AW (1994) Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am J Physiol 266:H1918–H1926

    CAS  PubMed  Google Scholar 

  66. McCurley A, Pires PW, Bender SB, Aronovitz M, Zhao MJ, Metzger D, Chambon P, Hill MA, Dorrance AM, Mendelsohn ME, Jaffe IZ (2012) Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med 18:1429–1433

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Meissner A, Yang J, Kroetsch JT, Sauve M, Dax H, Momen A, Noyan-Ashraf MH, Heximer S, Husain M, Lidington D, Bolz SS (2012) Tumor necrosis factor-alpha-mediated downregulation of the cystic fibrosis transmembrane conductance regulator drives pathological sphingosine-1-phosphate signaling in a mouse model of heart failure. Circulation 125:2739–2750

    CAS  PubMed  Google Scholar 

  68. Mendelsohn ME (2005) In hypertension, the kidney is not always the heart of the matter. J Clin Invest 115:840–844

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA (2005) Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 85:679–715

    CAS  PubMed  Google Scholar 

  70. Meyer JW, Flagella M, Sutliff RL, Lorenz JN, Nieman ML, Weber CS, Paul RJ, Shull GE (2002) Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl- cotransporter. Am J Physiol Heart Circ Physiol 283:H1846–H1855

    CAS  PubMed  Google Scholar 

  71. Miledi R (1982) A calcium-dependent transient outward current in Xenopus laevis oocytes. Proc R Soc Lond B Biol Sci 215:491–497

    CAS  PubMed  Google Scholar 

  72. Namkung W, Phuan PW, Verkman AS (2011) TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells. J Biol Chem 286:2365–2374

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Nelson MT, Conway MA, Knot HJ, Brayden JE (1997) Chloride channel blockers inhibit myogenic tone in rat cerebral arteries. J Physiol 502:259–264

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Orlov SN, Koltsova SV, Tremblay J, Baskakov MB, Hamet P (2012) NKCC1 and hypertension: role in the regulation of vascular smooth muscle contractions and myogenic tone. Ann Med 44(Suppl 1):S111–S118

    CAS  PubMed  Google Scholar 

  75. Owen NE (1984) Regulation of Na/K/Cl cotransport in vascular smooth muscle cells. Biochem Biophys Res Commun 125:500–508

    CAS  PubMed  Google Scholar 

  76. Pao AC (2014) Update on the Guytonian view of hypertension. Curr Opin Nephrol Hypertens 23:391–398

    CAS  PubMed  Google Scholar 

  77. Peng H, Matchkov V, Ivarsen A, Aalkjaer C, Nilsson H (2001) Hypothesis for the initiation of vasomotion. Circ Res 88:810–815

    CAS  PubMed  Google Scholar 

  78. Peotta VA, Bhandary P, Ogu U, Volk KA, Roghair RD (2014) Reduced blood pressure of CFTR-F508del carriers correlates with diminished arterial reactivity rather than circulating blood volume in mice. PLoS One 9:e96756

    PubMed Central  PubMed  Google Scholar 

  79. Pollock NS, Kargacin ME, Kargacin GJ (1998) Chloride channel blockers inhibit Ca2+ uptake by the smooth muscle sarcoplasmic reticulum. Biophys J 75:1759–1766

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Prasad V, Bodi I, Meyer JW, Wang Y, Ashraf M, Engle SJ, Doetschman T, Sisco K, Nieman ML, Miller ML, Lorenz JN, Shull GE (2008) Impaired cardiac contractility in mice lacking both the AE3 Cl-/HCO3 - exchanger and the NKCC1 Na+-K+-2Cl- cotransporter: effects on Ca2+ handling and protein phosphatases. J Biol Chem 283:31303–31314

    PubMed Central  CAS  PubMed  Google Scholar 

  81. Pritchard HA, Leblanc N, Albert AP, Greenwood IA (2014) Inhibitory role of phosphatidylinositol 4,5-bisphosphate on TMEM16A-encoded calcium-activated chloride channels in rat pulmonary artery. Br J Pharmacol 171:4311–4321

    CAS  PubMed  Google Scholar 

  82. Qiu Z, Dubin AE, Mathur J, Tu B, Reddy K, Miraglia LJ, Reinhardt J, Orth AP, Patapoutian A (2014) SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell 157:447–458

    CAS  PubMed  Google Scholar 

  83. Reho JJ, Zheng X, Fisher SA (2014) Smooth muscle contractile diversity in the control of regional circulations. Am J Physiol Heart Circ Physiol 306:H163–H172

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Howard HC, Mount DB, Rochefort D, Byun N, Dupré N, Lu J, Fan X, Song L, Rivière JB, Prévost C, Horst J, Simonati A, Lemcke B, Welch R, England R, Zhan FQ, Mercado A, Siesser WB, George AL Jr, McDonald MP, Bouchard JP, Mathieu J, Delpire E, Rouleau GA (2002) The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. Nat Genet 32(3):384–392

  85. Robert R, Norez C, Becq F (2005) Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl- transport of mouse aortic smooth muscle cells. J Physiol 568:483–495

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Robert R, Savineau JP, Norez C, Becq F, Guibert C (2007) Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries. Eur Respir J 30:857–864

    CAS  PubMed  Google Scholar 

  87. Rust MB, Faulhaber J, Budack MK, Pfeffer C, Maritzen T, Didie M, Beck FX, Boettger T, Schubert R, Ehmke H, Jentsch TJ, Hübner CA (2006) Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3. Circ Res 98:549–556

    CAS  PubMed  Google Scholar 

  88. Saitta M, Cavalier S, Garay R, Cragoe E Jr, Hannaert P (1990) Evidence for a DIOA-sensitive [K+, Cl-]-cotransport system in cultured vascular smooth muscle cells. Am J Hypertens 3:939–942

    CAS  PubMed  Google Scholar 

  89. Schleifenbaum J, Kassmann M, Szijarto IA, Hercule HC, Tano JY, Weinert S, Heidenreich M, Pathan AR, Anistan YM, Alenina N, Rusch NJ, Bader M, Jentsch TJ, Gollasch M (2014) Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ Res 115:263–272

    CAS  PubMed  Google Scholar 

  90. Schroeder BC, Cheng T, Jan YN, Jan LY (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Sheppard DN, Welsh MJ (1999) Structure and function of the CFTR chloride channel. Physiol Rev 79:S23–S45

    CAS  PubMed  Google Scholar 

  92. Shi XL, Wang GL, Zhang Z, Liu YJ, Chen JH, Zhou JG, Qiu QY, Guan YY (2007) Alteration of volume-regulated chloride movement in rat cerebrovascular smooth muscle cells during hypertension. Hypertension 49:1371–1377

    CAS  PubMed  Google Scholar 

  93. Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP (1996) Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet 13:183–188

    CAS  PubMed  Google Scholar 

  94. Sober S, Org E, Kepp K, Juhanson P, Eyheramendy S, Gieger C, Lichtner P, Klopp N, Veldre G, Viigimaa M, Doring A, Kooperative Gesundheitsforschung in der Region, Augsburg S, Putku M, Kelgo P, Study HYE, Shaw-Hawkins S, Howard P, Onipinla A, Dobson RJ, Newhouse SJ, Brown M, Dominiczak A, Connell J, Samani N, Farrall M, Study MRCBGoH, Caulfield MJ, Munroe PB, Illig T, Wichmann HE, Meitinger T, Laan M (2009) Targeting 160 candidate genes for blood pressure regulation with a genome-wide genotyping array. PLoS One 4:e6034

    PubMed Central  PubMed  Google Scholar 

  95. Stauber T, Jentsch TJ (2013) Chloride in vesicular trafficking and function. Annu Rev Physiol 75:453–477

    CAS  PubMed  Google Scholar 

  96. Stein V, Hermans-Borgmeyer I, Jentsch TJ, Hübner CA (2004) Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride. J Comp Neurol 468:57–64

    CAS  PubMed  Google Scholar 

  97. Sun H, Xia Y, Paudel O, Yang XR, Sham JS (2012) Chronic hypoxia-induced upregulation of Ca2+-activated Cl- channel in pulmonary arterial myocytes: a mechanism contributing to enhanced vasoreactivity. J Physiol 590:3507–3521

    PubMed Central  CAS  PubMed  Google Scholar 

  98. Super M, Irtiza-Ali A, Roberts SA, Schwarz M, Young M, Smith A, Roberts T, Hinks J, Heagerty A (2004) Blood pressure and the cystic fibrosis gene: evidence for lower pressure rises with age in female carriers. Hypertension 44:878–883

    CAS  PubMed  Google Scholar 

  99. Terashima H, Picollo A, Accardi A (2013) Purified TMEM16A is sufficient to form Ca2+-activated Cl- channels. Proc Natl Acad Sci U S A 110:19354–19359

    PubMed Central  CAS  PubMed  Google Scholar 

  100. Thomas-Gatewood C, Neeb ZP, Bulley S, Adebiyi A, Bannister JP, Leo MD, Jaggar JH (2011) TMEM16A channels generate Ca2+-activated Cl- currents in cerebral artery smooth muscle cells. Am J Physiol Heart Circ Physiol 301:H1819–H1827

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Vaughan-Jones RD (1979) Regulation of chloride in quiescent sheep-heart Purkinje fibres studied using intracellular chloride and pH-sensitive micro-electrodes. J Physiol 295:111–137

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Verkman AS, Galietta LJ (2009) Chloride channels as drug targets. Nat Rev Drug Discov 8:153–171

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Voss FK, Ullrich F, Munch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ (2014) Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science 344:634–638

    CAS  PubMed  Google Scholar 

  104. Wahlstrom BA (1973) Ionic fluxes in the rat portal vein and the applicability of the Goldman equation in predicting the membrane potential from flux data. Acta Physiol Scand 89:436–448

    CAS  PubMed  Google Scholar 

  105. Wahlstrom BA, Svennerholm B (1974) Potentiation and inhibition of noradrenaline induced contractions of the rat portal vein in anion substituted solutions. Acta Physiol Scand 92:404–411

    CAS  PubMed  Google Scholar 

  106. Wall SM, Knepper MA, Hassell KA, Fischer MP, Shodeinde A, Shin W, Pham TD, Meyer JW, Lorenz JN, Beierwaltes WH, Dietz JR, Shull GE, Kim YH (2006) Hypotension in NKCC1 null mice: role of the kidneys. Am J Physiol Renal Physiol 290:F409–F416

    CAS  PubMed  Google Scholar 

  107. Wang X, Breaks J, Loutzenhiser K, Loutzenhiser R (2007) Effects of inhibition of the Na+/K+/2Cl- cotransporter on myogenic and angiotensin II responses of the rat afferent arteriole. Am J Physiol Renal Physiol 292:F999–F1006

    CAS  PubMed  Google Scholar 

  108. Wang M, Yang H, Zheng LY, Zhang Z, Tang YB, Wang GL, Du YH, Lv XF, Liu J, Zhou JG, Guan YY (2012) Downregulation of TMEM16A calcium-activated chloride channel contributes to cerebrovascular remodeling during hypertension by promoting basilar smooth muscle cell proliferation. Circulation 125:697–707

    CAS  PubMed  Google Scholar 

  109. Welsh DG, Morielli AD, Nelson MT, Brayden JE (2002) Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90:248–250

    CAS  PubMed  Google Scholar 

  110. Yamazaki J, Duan D, Janiak R, Kuenzli K, Horowitz B, Hume JR (1998) Functional and molecular expression of volume-regulated chloride channels in canine vascular smooth muscle cells. J Physiol 507:729–736

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215

    CAS  PubMed  Google Scholar 

  112. Yu Y, Kuan AS, Chen TY (2014) Calcium-calmodulin does not alter the anion permeability of the mouse TMEM16A calcium-activated chloride channel. J Gen Physiol 144:115–124

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Yu K, Zhu J, Qu Z, Cui YY, Hartzell HC (2014) Activation of the Ano1 (TMEM16A) chloride channel by calcium is not mediated by calmodulin. J Gen Physiol 143:253–267

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Zhong XZ, Harhun MI, Olesen SP, Ohya S, Moffatt JD, Cole WC, Greenwood IA (2010) Participation of KCNQ (Kv7) potassium channels in myogenic control of cerebral arterial diameter. J Physiol 588:3277–3293

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Lidington D, Schubert R, Bolz SS (2013) Capitalizing on diversity: an integrative approach towards the multiplicity of cellular mechanisms underlying myogenic responsiveness. Cardiovasc Res 97(3):404–412

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Acknowledgments

This work was supported by grants of the DFG and the Else Kröner Fresenius-Stiftung to CAH, a grant of the Thyssen Stiftung to CAH and BCS, and a grant of the DZHK to HE.

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Authors and Affiliations

  1. Institut für Humangenetik, Universitätsklinikum Jena, Friedrich-Schiller Universität Jena, Kollegiengasse 10, 07743, Jena, Germany

    Christian A. Hübner

  2. Max-Delbrück Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany

    Björn C. Schroeder

  3. NeuroCure, Charitéplatz 1, 10117, Berlin, Germany

    Björn C. Schroeder

  4. Institut für Zelluläre und Integrative Physiologie, Universitätsklinikum Hamburg Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Heimo Ehmke

  5. Institut für Humangenetik, Universitätsklinikum Jena, Kollegiengasse 10, 07743, Jena, Germany

    Christian A. Hübner

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  1. Christian A. Hübner
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  2. Björn C. Schroeder
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  3. Heimo Ehmke
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Correspondence to Christian A. Hübner or Heimo Ehmke.

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Hübner, C.A., Schroeder, B.C. & Ehmke, H. Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle. Pflugers Arch - Eur J Physiol 467, 605–614 (2015). https://doi.org/10.1007/s00424-014-1684-y

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  • DOI: https://doi.org/10.1007/s00424-014-1684-y

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