Skip to main content

Advertisement

Log in

Biophysics and Physiology of the Volume-Regulated Anion Channel (VRAC)/Volume-Sensitive Outwardly Rectifying Anion Channel (VSOR)

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The volume-regulated anion channel (VRAC), also known as the volume-sensitive outwardly rectifying (VSOR) anion channel or the volume-sensitive organic osmolyte/anion channel (VSOAC), is essential for cell volume regulation after swelling in most vertebrate cell types studied to date. In addition to its role in cell volume homeostasis, VRAC has been implicated in numerous other physiological and pathophysiological processes, including cancer, ischemic brain edema, cell motility, proliferation, angiogenesis, programmed cell death, and excitotoxic glutamate release. Although VRAC has been extensively biophysically, pharmacologically, and functionally characterized, its molecular identity was highly controversial until the recent identification of the leucine-rich repeats containing 8A (LRRC8A) protein as essential for the VRAC current in multiple cell types and a likely pore-forming subunit of VRAC. Members of this distantly pannexin-1-related protein family form heteromers, and in addition to LRRC8A, at least another LRRC8 family member is required for the formation of a functional VRAC. This review summarizes the biophysical and pharmacological properties of VRAC, highlights its main physiological functions and pathophysiological implications, and outlines the search for its molecular identity.

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

Access this article

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

Similar content being viewed by others

References

  1. Hoffmann EK (1978) Regulation of cell volume by selective changes in the leak permeabilities of Ehrlich ascites tumor cells. Alfred Benzon Symp XI:397–417

    Google Scholar 

  2. Hoffmann EK, Simonsen LO, Lambert IH (1984) Volume-induced increase of K+ and Cl permeabilities in Ehrlich ascites tumor cells. Role of internal Ca2+. J Membr Biol 78:211–222

    Article  PubMed  CAS  Google Scholar 

  3. Hoffmann EK, Simonsen LO, Sjoholm C (1979) Membrane potential, chloride exchange, and chloride conductance in Ehrlich mouse ascites tumour cells. J Physiol 296:61–84

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Grinstein S, Clarke CA, Dupre A, Rothstein A (1982) Volume-induced increase of anion permeability in human lymphocytes. J Gen Physiol 80:801–823

    Article  PubMed  CAS  Google Scholar 

  5. Grinstein S, Clarke CA, Rothstein A (1982) Increased anion permeability during volume regulation in human lymphocytes. Philos Trans R Soc Lond B Biol Sci 299:509–518

    Article  PubMed  CAS  Google Scholar 

  6. Sarkadi B, Attisano L, Grinstein S, Buchwald M, Rothstein A (1984) Volume regulation of Chinese hamster ovary cells in anisoosmotic media. Biochim Biophys Acta 774:159–168

    Article  PubMed  CAS  Google Scholar 

  7. Cahalan MD, Lewis RS (1988) Role of potassium and chloride channels in volume regulation by T lymphocytes. Soc Gen Physiol Ser 43:281–301

    PubMed  CAS  Google Scholar 

  8. Hazama A, Okada Y (1988) Ca2+ sensitivity of volume-regulatory K+ and Cl channels in cultured human epithelial cells. J Physiol 402:687–702

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Nilius B, Oike M, Zahradnik I, Droogmans G (1994) Activation of a Cl current by hypotonic volume increase in human endothelial cells. J Gen Physiol 103:787–805

    Article  PubMed  CAS  Google Scholar 

  10. Nilius B, Droogmans G (2003) Amazing chloride channels: an overview. Acta Physiol Scand 177:119–147

    Article  PubMed  CAS  Google Scholar 

  11. Pedersen SF, Klausen TK, Nilius B (2015) The identification of a volume-regulated anion channel: an amazing Odyssey. Acta Physiol (Oxf) 213:868–881

    Article  CAS  Google Scholar 

  12. Stauber T (2015) The volume-regulated anion channel is formed by LRRC8 heteromers–molecular identification and roles in membrane transport and physiology. Biol Chem 396:975–990

    Article  PubMed  CAS  Google Scholar 

  13. Clapham DE (1998) The list of potential volume-sensitive chloride currents continues to swell (and shrink). J Gen Physiol 111:623–624

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Hoffmann EK, Lambert IH, Pedersen SF (2009) Physiology of cell volume regulation in vertebrates. Physiol Rev 89:193–277

    Article  PubMed  CAS  Google Scholar 

  15. Jentsch TJ, Stein V, Weinreich F, Zdebik AA (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568

    Article  PubMed  CAS  Google Scholar 

  16. Nilius B, Eggermont J, Voets T, Buyse G, Manolopoulos V, Droogmans G (1997) Properties of volume-regulated anion channels in mammalian cells. Prog Biophys Mol Biol 68:69–119

    Article  PubMed  CAS  Google Scholar 

  17. Okada Y (1997) Volume expansion-sensing outward-rectifier Cl- channel: fresh start to the molecular identity and volume sensor. Am J Physiol 273:C755–C789

    PubMed  CAS  Google Scholar 

  18. Strange K (1998) Molecular identity of the outwardly rectifying, swelling-activated anion channel: time to reevaluate pICln. J Gen Physiol 111:617–622

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Valverde MA, Diaz M, Sepulveda FV, Gill DR, Hyde SC, Higgins CF (1992) Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein. Nature 355:830–833

    Article  PubMed  CAS  Google Scholar 

  20. Paulmichl M, Li Y, Wickman K, Ackerman M, Peralta E, Clapham D (1992) New mammalian chloride channel identified by expression cloning. Nature 356:238–241

    Article  PubMed  CAS  Google Scholar 

  21. Duan D, Winter C, Cowley S, Hume JR, Horowitz B (1997) Molecular identification of a volume-regulated chloride channel. Nature 390:417–421

    Article  PubMed  CAS  Google Scholar 

  22. Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459

    PubMed  CAS  Google Scholar 

  23. Tominaga M, Tominaga T, Miwa A, Okada Y (1995) Volume-sensitive chloride channel activity does not depend on endogenous P-glycoprotein. J Biol Chem 270:27887–27893

    Article  PubMed  CAS  Google Scholar 

  24. De GC, Sehrer J, Viana F, van AK, Eggermont J, Mertens L, Raeymaekers L, Droogmans G, Nilius B (1995) Volume-activated chloride currents are not correlated with P-glycoprotein expression. Biochem J 307(Pt 3):713–718

    Google Scholar 

  25. Arreola J, Begenisich T, Nehrke K, Nguyen HV, Park K, Richardson L, Yang B, Schutte BC, Lamb FS, Melvin JE (2002) Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene. J Physiol 545:207–216

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Gong W, Xu H, Shimizu T, Morishima S, Tanabe S, Tachibe T, Uchida S, Sasaki S, Okada Y (2004) ClC-3-independent, PKC-dependent activity of volume-sensitive Cl channel in mouse ventricular cardiomyocytes. Cell Physiol Biochem 14:213–224

    Article  PubMed  CAS  Google Scholar 

  27. Stobrawa SM, Breiderhoff T, Takamori S, Engel D, Schweizer M, Zdebik AA, Bosl MR, Ruether K, Jahn H, Draguhn A, Jahn R, Jentsch TJ (2001) Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29:185–196

    Article  PubMed  CAS  Google Scholar 

  28. Pu WT, Krapivinsky GB, Krapivinsky L, Clapham DE (1999) pICln inhibits snRNP biogenesis by binding core spliceosomal proteins. Mol Cell Biol 19:4113–4120

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Pu WT, Wickman K, Clapham DE (2000) ICln is essential for cellular and early embryonic viability. J Biol Chem 275:12363–12366

    Article  PubMed  CAS  Google Scholar 

  30. Li C, Breton S, Morrison R, Cannon CL, Emma F, Sanchez-Olea R, Bear C, Strange K (1998) Recombinant pICln forms highly cation-selective channels when reconstituted into artificial and biological membranes. J Gen Physiol 112:727–736

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Garavaglia ML, Rodighiero S, Bertocchi C, Manfredi R, Furst J, Gschwentner M, Ritter M, Bazzini C, Botta G, Jakab M, Meyer G, Paulmichl M (2002) ICln channels reconstituted in heart-lipid bilayer are selective to chloride. Pflugers Arch 443:748–753

    Article  PubMed  CAS  Google Scholar 

  32. Haynes JK, Goldstein L (1993) Volume-regulatory amino acid transport in erythrocytes of the little skate, Raja erinacea. Am J Physiol 265:R173–R179

    PubMed  CAS  Google Scholar 

  33. Davis CE, Patel MK, Miller JR, John JE III, Jones LR, Tucker AL, Mounsey JP, Moorman JR (2004) Effects of phospholemman expression on swelling-activated ion currents and volume regulation in embryonic kidney cells. Neurochem Res 29:177–187

    Article  PubMed  CAS  Google Scholar 

  34. Moorman JR, Ackerman SJ, Kowdley GC, Griffin MP, Mounsey JP, Chen Z, Cala SE, O'Brian JJ, Szabo G, Jones LR (1995) Unitary anion currents through phospholemman channel molecules. Nature 377:737–740

    Article  PubMed  CAS  Google Scholar 

  35. Moorman JR, Jones LR (1998) Phospholemman: a cardiac taurine channel involved in regulation of cell volume. Adv Exp Med Biol 442:219–228

    Article  PubMed  CAS  Google Scholar 

  36. Dermietzel R, Hwang TK, Buettner R et al (1994) Cloning and in situ localization of a brain-derived porin that constitutes a large-conductance anion channel in astrocytic plasma membranes. Proc Natl Acad Sci U S A 91:499–503

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Landry D, Sullivan S, Nicolaides M, Redhead C, Edelman A, Field M, al-Awqati Q, Edwards J (1993) Molecular cloning and characterization of p64, a chloride channel protein from kidney microsomes. J Biol Chem 268:14948–14955

    PubMed  CAS  Google Scholar 

  38. Redhead CR, Edelman AE, Brown D, Landry DW, al-Awqati Q (1992) A ubiquitous 64-kDa protein is a component of a chloride channel of plasma and intracellular membranes. Proc Natl Acad Sci U S A 89:3716–3720

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Almaca J, Tian Y, Aldehni F, Ousingsawat J, Kongsuphol P, Rock JR, Harfe BD, Schreiber R, Kunzelmann K (2009) TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A. J Biol Chem 284:28571–28578

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Juul CA, Grubb S, Poulsen KA, Kyed T, Hashem N, Lambert IH, Larsen EH, Hoffmann EK (2014) Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca2+. Pflugers Arch 466:1899–1910

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Shimizu T, Iehara T, Sato K, Fujii T, Sakai H, Okada Y (2013) TMEM16F is a component of a Ca2+-activated Cl channel but not a volume-sensitive outwardly rectifying Cl- channel. Am J Physiol Cell Physiol 304:C748–C759

    Article  PubMed  CAS  Google Scholar 

  42. Yu K, Whitlock JM, Lee K, Ortlund EA, Cui YY, Hartzell HC (2015) Identification of a lipid scrambling domain in ANO6/TMEM16F. Elife 4:e06901

    PubMed  Google Scholar 

  43. Hammer C, Wanitchakool P, Sirianant L, Papiol S, Monnheimer M, Faria D, Ousingsawat J, Schramek N, Schmitt C, Margos G, Michel A, Kraiczy P, Pawlita M, Schreiber R, Schulz TF, Fingerle V, Tumani H, Ehrenreich H, Kunzelmann K (2015) A coding variant of ANO10, affecting volume regulation of macrophages, is associated with Borrelia seropositivity. Mol Med 21:26–37

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Kunzelmann K (2015) TMEM16, LRRC8A, bestrophin: chloride channels controlled by Ca2+ and cell volume. Trends Biochem Sci 40(535–543):2015

    Google Scholar 

  45. Chien LT, Hartzell HC (2007) Drosophila bestrophins are dually regulated by calcium and cell volume. J Gen Physiol 130:21A–22A

    Article  CAS  Google Scholar 

  46. Stotz SC, Clapham DE (2012) Anion-sensitive fluorophore identifies the Drosophila swell-activated chloride channel in a genome-wide RNA interference screen. PLoS ONE 7:e46865

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Chien LT, Hartzell HC (2008) Rescue of volume-regulated anion current by bestrophin mutants with altered charge selectivity. J Gen Physiol 132:537–546

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Milenkovic A, Brandl C, Milenkovic VM, Jendryke T, Sirianant L, Wanitchakool P, Zimmermann S, Reiff CM, Horling F, Schrewe H, Schreiber R, Kunzelmann K, Wetzel CH, Weber BH (2015) Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells. Proc Natl Acad Sci U S A 112:E2630–E2639

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Okada Y, Sato K, Numata T (2009) Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. J Physiol 587:2141–2149

    PubMed Central  PubMed  CAS  Google Scholar 

  50. Ise T, Shimizu T, Lee EL, Inoue H, Kohno K, Okada Y (2005) Roles of volume-sensitive Cl- channel in cisplatin-induced apoptosis in human epidermoid cancer cells. J Membr Biol 205:139–145

    Article  PubMed  CAS  Google Scholar 

  51. Maeno E, Ishizaki Y, Kanaseki T, Hazama A, Okada Y (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci U S A 97:9487–9492

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, Kucukosmanoglu A, Xu G, Voss FK, Reincke SM, Stauber T, Blomen VA, Vis DJ, Wessels LF, Brummelkamp TR, Borst P, Rottenberg S, Jentsch TJ (2015) Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J 34:2993–3008

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Shimizu T, Numata T, Okada Y (2004) A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl channel. Proc Natl Acad Sci U S A 101:6770–6773

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Akita T, Fedorovich SV, Okada Y (2011) Ca2+ nanodomain-mediated component of swelling-induced volume-sensitive outwardly rectifying anion current triggered by autocrine action of ATP in mouse astrocytes. Cell Physiol Biochem 28:1181–1190

    Article  PubMed  CAS  Google Scholar 

  55. Akita T, Okada Y (2011) Regulation of bradykinin-induced activation of volume-sensitive outwardly rectifying anion channels by Ca2+ nanodomains in mouse astrocytes. J Physiol 589:3909–3927

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  56. Akita T, Okada Y (2014) Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system. Neuroscience 275:211–231

    Article  PubMed  CAS  Google Scholar 

  57. Inoue H, Okada Y (2007) Roles of volume-sensitive chloride channel in excitotoxic neuronal injury. J Neurosci 27:1445–1455

    Article  PubMed  CAS  Google Scholar 

  58. Liu HT, Akita T, Shimizu T, Sabirov RZ, Okada Y (2009) Bradykinin-induced astrocyte-neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. J Physiol 587:2197–2209

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. 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

    Article  PubMed  CAS  Google Scholar 

  60. 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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Voets T, Nilius B, Vennekens R (2015) VRACs swallow platinum drugs. EMBO J 34:2985–2987

    Article  PubMed  CAS  Google Scholar 

  62. Nilius B, Prenen J, Voets T, Eggermont J, Droogmans G (1998) Activation of volume-regulated chloride currents by reduction of intracellular ionic strength in bovine endothelial cells. J Physiol 506(Pt 2):353–361

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Sabirov RZ, Prenen J, Tomita T, Droogmans G, Nilius B (2000) Reduction of ionic strength activates single volume-regulated anion channels (VRAC) in endothelial cells. Pflugers Arch 439:315–320

    Article  PubMed  CAS  Google Scholar 

  64. Voets T, Droogmans G, Raskin G, Eggermont J, Nilius B (1999) Reduced intracellular ionic strength as the initial trigger for activation of endothelial volume-regulated anion channels. Proc Natl Acad Sci U S A 96:5298–5303

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Kumar L, Chou J, Yee CS, Borzutzky A, Vollmann EH, von Andrian UH, Park SY, Hollander G, Manis JP, Poliani PL, Geha RS (2014) Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J Exp Med 211:929–942

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J (2003) A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest 112:1707–1713

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  67. Pedersen SF, Prenen J, Droogmans G, Hoffmann EK, Nilius B (1998) Separate swelling- and Ca2+-activated anion currents in Ehrlich ascites tumor cells. J Membr Biol 163:97–110

    Article  PubMed  CAS  Google Scholar 

  68. Strange K, Emma F, Jackson PS (1996) Cellular and molecular physiology of volume-sensitive anion channels. Am J Physiol 270:C711–C730

    PubMed  CAS  Google Scholar 

  69. Okada Y, Petersen CC, Kubo M, Morishima S, Tominaga M (1994) Osmotic swelling activates intermediate-conductance Cl channels in human intestinal epithelial cells. Jpn J Physiol 44:403–409

    Article  PubMed  CAS  Google Scholar 

  70. Jackson PS, Strange K (1995) Single-channel properties of a volume-sensitive anion conductance. Current activation occurs by abrupt switching of closed channels to an open state. J Gen Physiol 105:643–660

    Article  PubMed  CAS  Google Scholar 

  71. Jackson PS, Strange K (1996) Single channel properties of a volume sensitive anion channel: lessons from noise analysis. Kidney Int 49:1695–1699

    Article  PubMed  CAS  Google Scholar 

  72. Nilius B, Voets T, Eggermont J, Droogmans G (1999) VRAC: a multifunctional volume-regulated anion channel in vascular endothelium. In: Chloride channels. Oxford: Isis Medical Media Ltd

  73. Solc CK, Wine JJ (1991) Swelling-induced and depolarization-induced C1-channels in normal and cystic fibrosis epithelial cells. Am J Physiol 261:C658–C674

    PubMed  CAS  Google Scholar 

  74. Worrell RT, Butt AG, Cliff WH, Frizzell RA (1989) A volume-sensitive chloride conductance in human colonic cell line T84. Am J Physiol 256:C1111–C1119

    PubMed  CAS  Google Scholar 

  75. Voets T, Droogmans G, Nilius B (1997) Modulation of voltage-dependent properties of a swelling-activated Cl current. J Gen Physiol 110:313–325

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Hagiwara N, Masuda H, Shoda M, Irisawa H (1992) Stretch-activated anion currents of rabbit cardiac myocytes. J Physiol 456:285–302

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  77. Kubo M, Okada Y (1992) Volume-regulatory Cl channel currents in cultured human epithelial cells. J Physiol 456:351–371

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Rasola A, Galietta LJ, Gruenert DC, Romeo G (1992) Ionic selectivity of volume-sensitive currents in human epithelial cells. Biochim Biophys Acta 1139:319–323

    Article  PubMed  CAS  Google Scholar 

  79. Droogmans G, Maertens C, Prenen J, Nilius B (1999) Sulphonic acid derivatives as probes of pore properties of volume-regulated anion channels in endothelial cells. Br J Pharmacol 128:35–40

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Droogmans G, Prenen J, Eggermont J, Voets T, Nilius B (1998) Voltage-dependent block of endothelial volume-regulated anion channels by calix[4]arenes. Am J Physiol 275:C646–C652

    PubMed  CAS  Google Scholar 

  81. Ternovsky VI, Okada Y, Sabirov RZ (2004) Sizing the pore of the volume-sensitive anion channel by differential polymer partitioning. FEBS Lett 576:433–436

    Article  PubMed  CAS  Google Scholar 

  82. Kirk K, Ellory JC, Young JD (1992) Transport of organic substrates via a volume-activated channel. J Biol Chem 267:23475–23478

    PubMed  CAS  Google Scholar 

  83. Kirk K (1997) Swelling-activated organic osmolyte channels. J Membr Biol 158:1–16

    Article  PubMed  CAS  Google Scholar 

  84. Shennan DB (2008) Swelling-induced taurine transport: relationship with chloride channels, anion-exchangers and other swelling-activated transport pathways. Cell Physiol Biochem 21:15–28

    Article  PubMed  CAS  Google Scholar 

  85. Blum AE, Walsh BC, Dubyak GR (2010) Extracellular osmolarity modulates G protein-coupled receptor-dependent ATP release from 1321N1 astrocytoma cells. Am J Physiol Cell Physiol 298:C386–C396

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Burow P, Markwardt F (2014) When S1P meets ATP. Channels (Austin) 8:385–386

    Article  Google Scholar 

  87. Hisadome K, Koyama T, Kimura C, Droogmans G, Ito Y, Oike M (2002) Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells. J Gen Physiol 119:511–520

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  88. Tsumura T, Oiki S, Ueda S, Okuma M, Okada Y (1996) Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to extracellular nucleotides. Am J Physiol 271:C1872–C1878

    PubMed  CAS  Google Scholar 

  89. Lee CC, Freinkman E, Sabatini DM, Ploegh HL (2014) The protein synthesis inhibitor blasticidin s enters mammalian cells via leucine-rich repeat-containing protein 8D. J Biol Chem 289:17124–17131

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Helix N, Strobaek D, Dahl BH, Christophersen P (2003) Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293 cells by acidic di-aryl-ureas. J Membr Biol 196:83–94

    Article  PubMed  CAS  Google Scholar 

  91. Klausen TK, Bergdahl A, Hougaard C, Christophersen P, Pedersen SF, Hoffmann EK (2007) Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich Lettre ascites cells. J Cell Physiol 210:831–842

    Article  PubMed  CAS  Google Scholar 

  92. Abdullaev IF, Rudkouskaya A, Schools GP, Kimelberg HK, Mongin AA (2006) Pharmacological comparison of swelling-activated excitatory amino acid release and Cl currents in cultured rat astrocytes. J Physiol 572:677–689

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Decher T, Lang TJ, Nilius B, Bruggemann A, Busch TE, Steinmeyer K (2001) DCPIB is a novel selective blocker of I-Cl, I-swell and prevents swelling-induced shortening of guinea-pig atrial action potential duration. Br J Pharmacol 134:1467–1479

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  94. Harrigan TJ, Abdullaev IF, Jourd'heuil D, Mongin AA (2008) Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases. J Neurochem 106:2449–2462

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  95. Maertens C, Droogmans G, Verbesselt R, Nilius B (2002) Block of volume-regulated anion channels by selective serotonin reuptake inhibitors. Naunyn Schmiedebergs Arch Pharmacol 366:158–165

    Article  PubMed  CAS  Google Scholar 

  96. Maertens C, Wei L, Voets T, Droogmans G, Nilius B (1999) Block by fluoxetine of volume-regulated anion channels. Br J Pharmacol 126:508–514

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  97. Maertens C, Wei L, Droogmans G, Nilius B (2000) Inhibition of volume-regulated and calcium-activated chloride channels by the antimalarial mefloquine. J Pharmacol Exp Ther 295:29–36

    PubMed  CAS  Google Scholar 

  98. Maertens C, Droogmans G, Chakraborty P, Nilius B (2001) Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine. Br J Pharmacol 132:135–142

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  99. Nilius B, Prenen J, Kamouchi M, Viana F, Voets T, Droogmans G (1997) Inhibition by mibefradil, a novel calcium channel antagonist, of Ca2+- and volume-activated Cl channels in macrovascular endothelial cells. Br J Pharmacol 121:547–555

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  100. Poletto Chaves LA, Varanda WA (2008) Volume-activated chloride channels in mice Leydig cells. Pflugers Arch 457:493–504

    Article  PubMed  CAS  Google Scholar 

  101. Fan HT, Morishima S, Kida H, Okada Y (2001) Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl channels. Br J Pharmacol 133:1096–1106

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  102. Ye ZC, Oberheim N, Kettenmann H, Ransom BR (2009) Pharmacological “cross-inhibition” of connexin hemichannels and swelling activated anion channels. Glia 57:258–269

    Article  PubMed Central  PubMed  Google Scholar 

  103. Motais R, Guizouarn H, Garcia-Romeu F (1991) Red cell volume regulation: the pivotal role of ionic strength in controlling swelling-dependent transport systems. Biochim Biophys Acta 1075:169–180

    Article  PubMed  CAS  Google Scholar 

  104. Emma F, McManus M, Strange K (1997) Intracellular electrolytes regulate the volume set point of the organic osmolyte/anion channel VSOAC. Am J Physiol 272:C1766–C1775

    PubMed  CAS  Google Scholar 

  105. Strange K (1994) Are all cell volume changes the same? News Physiol Sci 9:223–228

    Google Scholar 

  106. Doroshenko P, Neher E (1992) Volume-sensitive chloride conductance in bovine chromaffin cell membrane. J Physiol 449:197–218

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  107. Voets T, Manolopoulos V, Eggermont J, Ellory C, Droogmans G, Nilius B (1998) Regulation of a swelling-activated chloride current in bovine endothelium by protein tyrosine phosphorylation and G proteins. J Physiol 506(Pt 2):341–352

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  108. Wang Y, Roman R, Lidofsky SD, Fitz JG (1996) Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation. Proc Natl Acad Sci U S A 93:12020–12025

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  109. Mongin AA, Kimelberg HK (2002) ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes. Am J Physiol Cell Physiol 283:C569–C578

    Article  PubMed  CAS  Google Scholar 

  110. Browe DM, Baumgarten CM (2004) Angiotensin II (AT1) receptors and NADPH oxidase regulate Cl current elicited by beta1 integrin stretch in rabbit ventricular myocytes. J Gen Physiol 124:273–287

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  111. Varela D, Simon F, Riveros A, Jorgensen F, Stutzin A (2004) NAD(P)H oxidase-derived H(2)O(2) signals chloride channel activation in cell volume regulation and cell proliferation. J Biol Chem 279:13301–13304

    Article  PubMed  CAS  Google Scholar 

  112. Ando-Akatsuka Y, Shimizu T, Numata T, Okada Y (2012) Involvements of the ABC protein ABCF2 and alpha-actinin-4 in regulation of cell volume and anion channels in human epithelial cells. J Cell Physiol 227:3498–3510

    Article  PubMed  CAS  Google Scholar 

  113. Burow P, Klapperstuck M, Markwardt F (2015) Activation of ATP secretion via volume-regulated anion channels by sphingosine-1-phosphate in RAW macrophages. Pflugers Arch 467:1215–1226

    Article  PubMed  CAS  Google Scholar 

  114. Klausen TK, Hougaard C, Hoffmann EK, Pedersen SF (2006) Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. Am J Physiol Cell Physiol 291:C757–C771

    Article  PubMed  CAS  Google Scholar 

  115. Nilius B, Voets T, Prenen J, Barth H, Aktories K, Kaibuchi K, Droogmans G, Eggermont J (1999) Role of Rho and Rho kinase in the activation of volume-regulated anion channels in bovine endothelial cells. J Physiol 516(Pt 1):67–74

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  116. Pedersen SF, Beisner KH, Hougaard C, Willumsen BM, Lambert IH, Hoffmann EK (1992) Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts. J Physiol 541:779–796

    Article  CAS  Google Scholar 

  117. Tilly BC, Edixhoven MJ, Tertoolen LG, Morii N, Saitoh Y, Narumiya S, de Jonge HR (1996) Activation of the osmo-sensitive chloride conductance involves P21rho and is accompanied by a transient reorganization of the F-actin cytoskeleton. Mol Biol Cell 7:1419–1427

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  118. Feranchak AP, Roman RM, Schwiebert EM, Fitz JG (1998) Phosphatidylinositol 3-kinase contributes to cell volume regulation through effects on ATP release. J Biol Chem 273:14906–14911

    Article  PubMed  CAS  Google Scholar 

  119. Carton I, Trouet D, Hermans D, Barth H, Aktories K, Droogmans G, Jorgensen NK, Hoffmann EK, Nilius B, Eggermont J (2002) RhoA exerts a permissive effect on volume-regulated anion channels in vascular endothelial cells. Am J Physiol Cell Physiol 283:C115–C125

    Article  PubMed  CAS  Google Scholar 

  120. Du XL, Gao Z, Lau CP, Chiu SW, Tse HF, Baumgarten CM, Li GR (2004) Differential effects of tyrosine kinase inhibitors on volume-sensitive chloride current in human atrial myocytes: evidence for dual regulation by Src and EGFR kinases. J Gen Physiol 123:427–439

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  121. Lepple-Wienhues A, Szabo I, Laun T, Kaba NK, Gulbins E, Lang F (1998) The tyrosine kinase p56lck mediates activation of swelling-induced chloride channels in lymphocytes. J Cell Biol 141:281–286

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  122. Tilly BC, den Van BN, Tertoolen LG, Edixhoven MJ, de Jonge HR (1993) Protein tyrosine phosphorylation is involved in osmoregulation of ionic conductances. J Biol Chem 268:19919–19922

    PubMed  CAS  Google Scholar 

  123. Levitan I, Christian AE, Tulenko TN, Rothblat GH (2000) Membrane cholesterol content modulates activation of volume-regulated anion current in bovine endothelial cells. J Gen Physiol 115:405–416

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  124. Romanenko VG, Rothblat GH, Levitan I (2004) Sensitivity of volume-regulated anion current to cholesterol structural analogues. J Gen Physiol 123:77–87

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  125. Nilius B, Gerke V, Prenen J, Szucs G, Heinke S, Weber K, Droogmans G (1996) Annexin II modulates volume-activated chloride currents in vascular endothelial cells. J Biol Chem 271:30631–30636

    Article  PubMed  CAS  Google Scholar 

  126. Trouet D, Hermans D, Droogmans G, Nilius B, Eggermont J (2001) Inhibition of volume-regulated anion channels by dominant-negative caveolin-1. Biochem Biophys Res Commun 284:461–465

    Article  PubMed  CAS  Google Scholar 

  127. Trouet D, Nilius B, Jacobs A, Remacle C, Droogmans G, Eggermont J (1999) Caveolin-1 modulates the activity of the volume-regulated chloride channel. J Physiol 520(Pt 1):113–119

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  128. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D (1998) Functional significance of cell volume regulatory mechanisms. Physiol Rev 78:247–306

    PubMed  CAS  Google Scholar 

  129. Wehner F, Olsen H, Tinel H, Kinne-Saffran E, Kinne RKH (2003) Cell volume regulation: osmolytes, osmolyte transport, and signal transduction. Rev Physiol Biochem Pharmacol 148:1–80

    PubMed  CAS  Google Scholar 

  130. Forsyth SE, Hoger A, Hoger JH (1997) Molecular cloning and expression of a bovine endothelial inward rectifier potassium channel. FEBS Lett 409:277–282

    Article  PubMed  CAS  Google Scholar 

  131. Kamouchi M, Trouet D, De GC, Droogmans G, Eggermont J, Nilius B (1997) Functional effects of expression of hslo Ca2+ activated K+ channels in cultured macrovascular endothelial cells. Cell Calcium 22:497–506

    Article  PubMed  CAS  Google Scholar 

  132. Voets T, Droogmans G, Nilius B (1996) Membrane currents and the resting membrane potential in cultured bovine pulmonary artery endothelial cells. J Physiol 497(Pt 1):95–107

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  133. Shimizu T, Maeno E, Okada Y (2007) Prerequisite role of persistent cell shrinkage in apoptosis of human epithelial cells. Sheng Li Xue Bao 59:512–516

    PubMed  CAS  Google Scholar 

  134. Okada Y, Maeno E, Shimizu T, Dezaki K, Wang J, Morishima S (2001) Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD). J Physiol-Lond 532:3–16

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  135. Okada Y, Shimizu T, Maeno E, Tanabe S, Wang X, Takahashi N (2006) Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death. J Membr Biol 209:21–29

    Article  PubMed  CAS  Google Scholar 

  136. Tanabe S, Wang X, Takahashi N, Uramoto H, Okada Y (2005) HCO3 -independent rescue from apoptosis by stilbene derivatives in rat cardiomyocytes. FEBS Lett 579:517–522

    Article  PubMed  CAS  Google Scholar 

  137. Wang X, Takahashi N, Uramoto H, Okada Y (2005) Chloride channel inhibition prevents ROS-dependent apoptosis induced by ischemia-reperfusion in mouse cardiomyocytes. Cell Physiol Biochem 16:147–154

    Article  PubMed  CAS  Google Scholar 

  138. Inoue H, Ohtaki H, Nakamachi T, Shioda S, Okada Y (2007) Anion channel blockers attenuate delayed neuronal cell death induced by transient forebrain ischemia. J Neurosci Res 85:1427–1435

    Article  PubMed  CAS  Google Scholar 

  139. Maeno E, Shimizu T, Okada Y (2006) Normotonic cell shrinkage induces apoptosis under extracellular low Cl conditions in human lymphoid and epithelial cells. Acta Physiol (Oxf) 187:217–222

    Article  CAS  Google Scholar 

  140. Nukui M, Shimizu T, Okada Y (2006) Normotonic cell shrinkage induced by Na+ deprivation results in apoptotic cell death in human epithelial HeLa cells. J Physiol Sci 56:335–339

    Article  PubMed  CAS  Google Scholar 

  141. Lee EL, Shimizu T, Ise T, Numata T, Kohno K, Okada Y (2007) Impaired activity of volume-sensitive Cl- channel is involved in cisplatin resistance of cancer cells. J Cell Physiol 211:513–521

    Article  PubMed  CAS  Google Scholar 

  142. Poulsen KA, Andersen EC, Hansen CF, Klausen TK, Hougaard C, Lambert IH, Hoffmann EK (2010) Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels. Am J Physiol Cell Physiol 298:C14–C25

    Article  PubMed  CAS  Google Scholar 

  143. Sorensen BH, Thorsteinsdottir UA, Lambert IH (2014) Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate. Am J Physiol Cell Physiol 307:C1071–C1080

    Article  PubMed  CAS  Google Scholar 

  144. Dezaki K, Maeno E, Sato K, Akita T, Okada Y (2012) Early-phase occurrence of K+ and Cl- efflux in addition to Ca2+ mobilization is a prerequisite to apoptosis in HeLa cells. Apoptosis 17:821–831

    Article  PubMed  CAS  Google Scholar 

  145. Szabo I, Lepple-Wienhues A, Kaba KN, Zoratti M, Gulbins E, Lang F (1998) Tyrosine kinase-dependent activation of a chloride channel in CD95-induced apoptosis in T lymphocytes. Proc Natl Acad Sci U S A 95:6169–6174

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  146. Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ, Lander ES, Sabatini DM (2015) Identification and characterization of essential genes in the human genome. Science 350:1096–1101

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  147. Banderali U, Roy G (1992) Anion channels for amino acids in MDCK cells. Am J Physiol 263:C1200–C1207

    PubMed  CAS  Google Scholar 

  148. Hyzinski-Garcia MC, Rudkouskaya A, Mongin AA (2014) LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes. J Physiol 592:4855–4862

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  149. Jackson PS, Strange K (1993) Volume-sensitive anion channels mediate swelling-activated inositol and taurine efflux. Am J Physiol 265:C1489–C1500

    PubMed  CAS  Google Scholar 

  150. Kimelberg HK, Goderie SK, Higman S, Pang S, Waniewski RA (1990) Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures. J Neurosci 10:1583–1591

    PubMed  CAS  Google Scholar 

  151. Mulligan SJ, MacVicar BA (2006) VRACs CARVe a path for novel mechanisms of communication in the CNS. Sci STKE 2006:e42

    Article  Google Scholar 

  152. Kimelberg HK (2005) Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy. Glia 50:389–397

    Article  PubMed  Google Scholar 

  153. Kimelberg HK, MacVicar BA, Sontheimer H (2006) Anion channels in astrocytes: biophysics, pharmacology, and function. Glia 54:747–757

    Article  PubMed Central  PubMed  Google Scholar 

  154. Mongin AA (2007) Disruption of ionic and cell volume homeostasis in cerebral ischemia: the perfect storm. Pathophysiology 14:183–193

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  155. Barros LF, Hermosilla T, Castro J (2001) Necrotic volume increase and the early physiology of necrosis. Comp Biochem Physiol A Mol Integr Physiol 130:401–409

    Article  PubMed  CAS  Google Scholar 

  156. Olney JW (1990) Excitotoxicity: an overview. Can Dis Wkly Rep 16 Suppl 1E: 47–57

  157. Hasbani MJ, Hyrc KL, Faddis BT, Romano C, Goldberg MP (1998) Distinct roles for sodium, chloride, and calcium in excitotoxic dendritic injury and recovery. Exp Neurol 154:241–258

    Article  PubMed  CAS  Google Scholar 

  158. Doroshenko P, Sabanov V, Doroshenko N (2001) Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts. J Cell Physiol 187:65–72

    Article  PubMed  CAS  Google Scholar 

  159. Klausen TK, Preisler S, Pedersen SF, Hoffmann EK (2010) Monovalent ions control proliferation of Ehrlich Lettre ascites cells. Am J Physiol Cell Physiol 299:C714–C725

    Article  PubMed  CAS  Google Scholar 

  160. Shen MR, Droogmans G, Eggermont J, Voets T, Ellory JC, Nilius B (2000) Differential expression of volume-regulated anion channels during cell cycle progression of human cervical cancer cells. J Physiol 529(Pt 2):385–394

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  161. Voets T, Szucs G, Droogmans G, Nilius B (1995) Blockers of volume-activated Cl currents inhibit endothelial cell proliferation. Pflugers Arch 431:132–134

    Article  PubMed  CAS  Google Scholar 

  162. Chen L, Wang L, Zhu L, Nie S, Zhang J, Zhong P, Cai B, Luo H, Jacob TJ (2002) Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells. Am J Physiol Cell Physiol 283:C1313–C1323

    Article  PubMed  CAS  Google Scholar 

  163. Nilius B (2001) Chloride channels go cell cycling. J Physiol 532:581

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  164. Voets T, Wei L, De SP, van DW, Eggermont J, Droogmans G, Nilius B (1997) Downregulation of volume-activated Cl currents during muscle differentiation. Am J Physiol 272:C667–C674

    PubMed  CAS  Google Scholar 

  165. Urrego D, Tomczak AP, Zahed F, Stuhmer W, Pardo LA (2014) Potassium channels in cell cycle and cell proliferation. Philos Trans R Soc Lond B Biol Sci 369:20130094

    Article  PubMed Central  PubMed  Google Scholar 

  166. Ginzberg MB, Kafri R, Kirschner M (2015) Cell biology. On being the right (cell) size. Science 348:1245075

    Article  PubMed  CAS  Google Scholar 

  167. Habela CW, Sontheimer H (2007) Cytoplasmic volume condensation is an integral part of mitosis. Cell Cycle 6:1613–1620

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  168. Pendergrass WR, Angello JC, Kirschner MD, Norwood TH (1991) The relationship between the rate of entry into S phase, concentration of DNA polymerase alpha, and cell volume in human diploid fibroblast-like monokaryon cells. Exp Cell Res 192:418–425

    Article  PubMed  CAS  Google Scholar 

  169. Rouzaire-Dubois B, Malo M, Milandri JB, Dubois JM (2004) Cell size-proliferation relationship in rat glioma cells. Glia 45:249–257

    Article  PubMed  Google Scholar 

  170. Rouzaire-Dubois B, Milandri JB, Bostel S, Dubois JM (2000) Control of cell proliferation by cell volume alterations in rat C6 glioma cells. Pflugers Arch 440:881–888

    Article  PubMed  CAS  Google Scholar 

  171. Mao J, Wang L, Fan A, Wang J, Xu B, Jacob TJ, Chen L (2007) Blockage of volume-activated chloride channels inhibits migration of nasopharyngeal carcinoma cells. Cell Physiol Biochem 19:249–258

    Article  PubMed  CAS  Google Scholar 

  172. Ransom CB, O'Neal JT, Sontheimer H (2001) Volume-activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells. J Neurosci 21:7674–7683

    PubMed  CAS  Google Scholar 

  173. Schneider L, Klausen TK, Stock C, Mally S, Christensen ST, Pedersen SF, Hoffmann EK, Schwab A (2008) H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts. Pflugers Arch 455:1055–1062

    Article  PubMed  CAS  Google Scholar 

  174. Soroceanu L, Manning TJ Jr, Sontheimer H (1999) Modulation of glioma cell migration and invasion using Cl and K+ ion channel blockers. J Neurosci 19:5942–5954

    PubMed  CAS  Google Scholar 

  175. Schwab A, Fabian A, Hanley PJ, Stock C (2012) Role of ion channels and transporters in cell migration. Physiol Rev 92:1865–1913

    Article  PubMed  CAS  Google Scholar 

  176. Manolopoulos VG, Liekens S, Koolwijk P, Voets T, Peters E, Droogmans G, Lelkes PI, De CE, Nilius B (2000) Inhibition of angiogenesis by blockers of volume-regulated anion channels. Gen Pharmacol 34:107–116

    Article  PubMed  CAS  Google Scholar 

  177. Ziegelhoeffer T, Scholz D, Friedrich C, Helisch A, Wagner S, Fernandez B, Schaper W (2003) Inhibition of collateral artery growth by mibefradil: possible role of volume-regulated chloride channels. Endothelium 10:237–246

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work in the author’s laboratories is supported by grants from the Danish Council for Independent Research and the Kirsten and Freddy Johansen Foundation (SFP) as well as by JSPS KAKENHI grants (YO).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stine F. Pedersen.

Additional information

This article is published as part of the Special Issue on: “Molecular physiology of anion channels: dual function proteins and new structural motifs”

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pedersen, S.F., Okada, Y. & Nilius, B. Biophysics and Physiology of the Volume-Regulated Anion Channel (VRAC)/Volume-Sensitive Outwardly Rectifying Anion Channel (VSOR). Pflugers Arch - Eur J Physiol 468, 371–383 (2016). https://doi.org/10.1007/s00424-015-1781-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-015-1781-6

Keywords

Navigation