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How is the highly positive endocochlear potential formed? The specific architecture of the stria vascularis and the roles of the ion-transport apparatus

  • Sensory Physiology
  • Published:
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Abstract

Cochlear endolymph, an extracellular solution containing 150 mM K+, exhibits a positive potential of +80 mV. This is called the endocochlear potential (EP) and is essential for audition. The mechanism responsible for formation of the EP has been an enigma for the half century since its first measurement. A key element is the stria vascularis, which displays a characteristic tissue structure and expresses multiple ion-transport apparatus. The stria comprises two epithelial layers: a layer of marginal cells and one composed of intermediate and basal cells. Between the two layers lies an extracellular space termed the intrastrial space (IS), which is thus surrounded by the apical membranes of intermediate cells and the basolateral membranes of marginal cells. The fluid in the IS exhibits a low concentration of K+ and a positive potential similar to the EP. We have demonstrated that the IS is electrically isolated from the neighboring extracellular fluids, perilymph, and endolymph, which allows the IS to sustain its positive potential. This IS potential is generated by K+ diffusion across the apical membranes of intermediate cells, where inwardly rectifying Kir4.1 channels are localized. The low K+ concentration in the IS, which is mandatory for the large K+-diffusion potential, is maintained by Na+,K+-ATPases and Na+,K+,2Cl−-cotransporters expressed at the basolateral membranes of marginal cells. An additional K+-diffusion potential formed by KCNQ1/KCNE1-K+ channels at the apical membranes of marginal cells also contributes to the EP. Therefore, the EP depends on an electrically isolated space and two K+-diffusion potentials in the stria vascularis.

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References

  1. Ando M, Takeuchi S (1999) Immunological identification of an inward rectifier K+ channel (Kir4.1) in the intermediate cell (melanocyte) of the cochlear stria vascularis of gerbils and rats. Cell Tissue Res 298:179–183

    CAS  PubMed  Google Scholar 

  2. Ando M, Takeuchi S (2000) mRNA encoding 'ClC-K1, a kidney Cl− channel' is expressed in marginal cells of the stria vascularis of rat cochlea: its possible contribution to Cl− currents. Neurosci Lett 284:171–174

    CAS  PubMed  Google Scholar 

  3. Beisel KW, Rocha-Sanchez SM, Morris KA, Nie L, Feng F, Kachar B, Yamoah EN, Fritzsch B (2005) Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss. J Neurosci 25:9285–9293

    CAS  PubMed  Google Scholar 

  4. Birkenhager R, Otto E, Schurmann MJ, Vollmer M, Ruf EM, Maier-Lutz I, Beekmann F, Fekete A, Omran H, Feldmann D, Milford DV, Jeck N, Konrad M, Landau D, Knoers NV, Antignac C, Sudbrak R, Kispert A, Hildebrandt F (2001) Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet 29:310–314

    CAS  PubMed  Google Scholar 

  5. Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van't Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360:1960–1970

    CAS  PubMed  Google Scholar 

  6. Boettger T, Hubner CA, Maier H, Rust MB, Beck FX, Jentsch TJ (2002) Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4. Nature 416:874–878

    CAS  PubMed  Google Scholar 

  7. 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, Hubner CA, Jentsch TJ (2003) Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. Embo J 22:5422–5434

    CAS  PubMed  Google Scholar 

  8. Cable J, Steel KP (1998) Combined cochleo-saccular and neuroepithelial abnormalities in the Varitint-waddler-J (VaJ) mouse. Hear Res 123:125–136

    CAS  PubMed  Google Scholar 

  9. Casimiro MC, Knollmann BC, Ebert SN, Vary JC Jr, Greene AE, Franz MR, Grinberg A, Huang SP, Pfeifer K (2001) Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome. Proc Natl Acad Sci U S A 98:2526–2531

    CAS  PubMed  Google Scholar 

  10. Chan DK, Hudspeth AJ (2005) Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro. Nat Neurosci 8:149–155

    CAS  PubMed  Google Scholar 

  11. Cohen-Salmon M, Regnault B, Cayet N, Caille D, Demuth K, Hardelin JP, Janel N, Meda P, Petit C (2007) Connexin30 deficiency causes instrastrial fluid–blood barrier disruption within the cochlear stria vascularis. Proc Natl Acad Sci U S A 104:6229–6234

    CAS  PubMed  Google Scholar 

  12. Crouch JJ, Sakaguchi N, Lytle C, Schulte BA (1997) Immunohistochemical localization of the Na-K-Cl co-transporter (NKCC1) in the gerbil inner ear. J Histochem Cytochem 45:773–778

    CAS  PubMed  Google Scholar 

  13. Cuajungco MP, Grimm C, Heller S (2007) TRP channels as candidates for hearing and balance abnormalities in vertebrates. Biochim Biophys Acta 1772:1022–1027

    CAS  PubMed  Google Scholar 

  14. Dallos P, Fakler B (2002) Prestin, a new type of motor protein. Nat Rev Mol Cell Biol 3:104–111

    CAS  PubMed  Google Scholar 

  15. Delpire E, Lu J, England R, Dull C, Thorne T (1999) Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Nat Genet 22:192–195

    CAS  PubMed  Google Scholar 

  16. Di Palma F, Belyantseva IA, Kim HJ, Vogt TF, Kachar B, Noben-Trauth K (2002) Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc Natl Acad Sci U S A 99:14994–14999

    PubMed  Google Scholar 

  17. Dixon MJ, Gazzard J, Chaudhry SS, Sampson N, Schulte BA, Steel KP (1999) Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice. Hum Mol Genet 8:1579–1584

    CAS  PubMed  Google Scholar 

  18. Dulon D, Sugasawa M, Blanchet C, Erostegui C (1995) Direct measurements of Ca2+-activated K+ currents in inner hair cells of the guinea-pig cochlea using photolabile Ca2+ chelators. Pflugers Arch 430:365–373

    CAS  PubMed  Google Scholar 

  19. Estevez R, Boettger T, Stein V, Birkenhager R, Otto E, Hildebrandt F, Jentsch TJ (2001) Barttin is a Cl− channel beta-subunit crucial for renal Cl− reabsorption and inner ear K+ secretion. Nature 414:558–561

    CAS  PubMed  Google Scholar 

  20. Flagella M, Clarke LL, Miller ML, Erway LC, Giannella RA, Andringa A, Gawenis LR, Kramer J, Duffy JJ, Doetschman T, Lorenz JN, Yamoah EN, Cardell EL, Shull GE (1999) Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J Biol Chem 274:26946–26955

    CAS  PubMed  Google Scholar 

  21. Geleoc GS, Lennan GW, Richardson GP, Kros CJ (1997) A quantitative comparison of mechanoelectrical transduction in vestibular and auditory hair cells of neonatal mice. Proc Biol Sci 264:611–621

    CAS  PubMed  Google Scholar 

  22. Gow A, Davies C, Southwood CM, Frolenkov G, Chrustowski M, Ng L, Yamauchi D, Marcus DC, Kachar B (2004) Deafness in Claudin 11-null mice reveals the critical contribution of basal cell tight junctions to stria vascularis function. J Neurosci 24:7051–7062

    CAS  PubMed  Google Scholar 

  23. Grimm C, Cuajungco MP, van Aken AF, Schnee M, Jors S, Kros CJ, Ricci AJ, Heller S (2007) A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. Proc Natl Acad Sci U S A 104:19583–19588

    CAS  PubMed  Google Scholar 

  24. Hama K, Saito K (1977) Gap junctions between the supporting cells in some acoustico-vestibular receptors. J Neurocytol 6:1–12

    CAS  PubMed  Google Scholar 

  25. Hibino H, Higashi-Shingai K, Fujita A, Iwai K, Ishii M, Kurachi Y (2004) Expression of an inwardly rectifying K+ channel, Kir5.1, in specific types of fibrocytes in the cochlear lateral wall suggests its functional importance in the establishment of endocochlear potential. Eur J Neurosci 19:76–84

    PubMed  Google Scholar 

  26. Hibino H, Horio Y, Inanobe A, Doi K, Ito M, Yamada M, Gotow T, Uchiyama Y, Kawamura M, Kubo T, Kurachi Y (1997) An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4.1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential. J Neurosci 17:4711–4721

    CAS  PubMed  Google Scholar 

  27. Hibino H, Kurachi Y (2006) Molecular and physiological bases of the K+ circulation in the mammalian inner ear. Physiology (Bethesda) 21:336–345

    CAS  Google Scholar 

  28. Hinojosa R, Rodriguez-Echandia EL (1966) The fine structure of the stria vascularis of the cat inner ear. Am J Anat 118:631–663

    CAS  PubMed  Google Scholar 

  29. Hudspeth AJ (1989) How the ear's works work. Nature 341:397–404

    CAS  PubMed  Google Scholar 

  30. Hudspeth AJ (1997) How hearing happens. Neuron 19:947–950

    CAS  PubMed  Google Scholar 

  31. Hudspeth AJ (2008) Making an effort to listen: mechanical amplification in the ear. Neuron 59:530–545

    CAS  PubMed  Google Scholar 

  32. Hudspeth AJ, Corey DP (1977) Sensitivity, polarity, and conductance change in the response of vertebrate hair cells to controlled mechanical stimuli. Proc Natl Acad Sci U S A 74:2407–2411

    CAS  PubMed  Google Scholar 

  33. Ikeda K, Morizono T (1989) Electrochemical profiles for monovalent ions in the stria vascularis: cellular model of ion transport mechanisms. Hear Res 39:279–286

    CAS  PubMed  Google Scholar 

  34. Iwano T, Yamamoto A, Omori K, Akayama M, Kumazawa T, Tashiro Y (1989) Quantitative immunocytochemical localization of Na+, K+-ATPase alpha-subunit in the lateral wall of rat cochlear duct. J Histochem Cytochem 37:353–363

    CAS  PubMed  Google Scholar 

  35. Jahnke K (1975) The fine structure of freeze-fractured intercellular junctions in the guinea pig inner ear. Acta Otolaryngol Suppl 336:1–40

    CAS  PubMed  Google Scholar 

  36. Keating MT, Sanguinetti MC (2001) Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104:569–580

    CAS  PubMed  Google Scholar 

  37. Kennedy HJ, Evans MG, Crawford AC, Fettiplace R (2003) Fast adaptation of mechanoelectrical transducer channels in mammalian cochlear hair cells. Nat Neurosci 6:832–836

    CAS  PubMed  Google Scholar 

  38. Kerr TP, Ross MD, Ernst SA (1982) Cellular localization of Na+, K+-ATPase in the mammalian cochlear duct: significance for cochlear fluid balance. Am J Otolaryngol 3:332–338

    CAS  PubMed  Google Scholar 

  39. Kharkovets T, Dedek K, Maier H, Schweizer M, Khimich D, Nouvian R, Vardanyan V, Leuwer R, Moser T, Jentsch TJ (2006) Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness. Embo J 25:642–652

    CAS  PubMed  Google Scholar 

  40. Kikuchi T, Adams JC, Miyabe Y, So E, Kobayashi T (2000) Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness. Med Electron Microsc 33:51–56

    CAS  PubMed  Google Scholar 

  41. Kikuchi T, Kimura RS, Paul DL, Adams JC (1995) Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol (Berl) 191:101–118

    CAS  Google Scholar 

  42. Kitajiri S, Miyamoto T, Mineharu A, Sonoda N, Furuse K, Hata M, Sasaki H, Mori Y, Kubota T, Ito J, Furuse M, Tsukita S (2004) Compartmentalization established by claudin-11-based tight junctions in stria vascularis is required for hearing through generation of endocochlear potential. J Cell Sci 117:5087–5096

    CAS  PubMed  Google Scholar 

  43. Kitajiri SI, Furuse M, Morita K, Saishin-Kiuchi Y, Kido H, Ito J, Tsukita S (2004) Expression patterns of claudins, tight junction adhesion molecules, in the inner ear. Hear Res 187:25–34

    CAS  PubMed  Google Scholar 

  44. Konishi T, Butler RA, Fernandez C (1961) Effect of anoxia on cochlear potentials. J Acoust Soc Amer 33:349–390

    Google Scholar 

  45. Konishi T, Hamrick PE, Walsh PJ (1978) Ion transport in guinea pig cochlea. I. Potassium and sodium transport. Acta Otolaryngol 86:22–34

    CAS  PubMed  Google Scholar 

  46. Konishi T, Mendelsohn M (1970) Effect of ouabain on cochlear potentials and endolymph composition in guinea pigs. Acta Otolaryngol 69:192–199

    CAS  PubMed  Google Scholar 

  47. Kros CJ, Ruppersberg JP, Rusch A (1998) Expression of a potassium current in inner hair cells during development of hearing in mice. Nature 394:281–284

    CAS  PubMed  Google Scholar 

  48. Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (1999) KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96:437–446

    CAS  PubMed  Google Scholar 

  49. Kuijpers W, Bonting SL (1970) The cochlear potentials. I. The effect of ouabain on the cochlear potentials of the guinea pig. Pflugers Arch 320:348–358

    CAS  PubMed  Google Scholar 

  50. Kuijpers W, Bonting SL (1970) The cochlear potentials. II. The nature of the cochlear endolymphatic resting potential. Pflugers Arch 320:359–372

    CAS  PubMed  Google Scholar 

  51. Kusakari J, Ise I, Comegys TH, Thalmann I, Thalmann R (1978) Effect of ethacrynic acid, furosemide, and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis. Laryngoscope 88:12–37

    CAS  PubMed  Google Scholar 

  52. Langer P, Grunder S, Rusch A (2003) Expression of Ca2+-activated BK channel mRNA and its splice variants in the rat cochlea. J Comp Neurol 455:198–209

    CAS  PubMed  Google Scholar 

  53. Lautermann J, Frank HG, Jahnke K, Traub O, Winterhager E (1999) Developmental expression patterns of connexin26 and -30 in the rat cochlea. Dev Genet 25:306–311

    CAS  PubMed  Google Scholar 

  54. Lautermann J, ten Cate WJ, Altenhoff P, Grummer R, Traub O, Frank H, Jahnke K, Winterhager E (1998) Expression of the gap-junction connexins 26 and 30 in the rat cochlea. Cell Tissue Res 294:415–420

    CAS  PubMed  Google Scholar 

  55. Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103:525–535

    CAS  PubMed  Google Scholar 

  56. Mammano F, Bortolozzi M, Ortolano S, Anselmi F (2007) Ca2+ signaling in the inner ear. Physiology (Bethesda) 22:131–144

    CAS  Google Scholar 

  57. Marcus DC (1984) Characterization of potassium permeability of cochlear duct by perilymphatic perfusion of barium. Am J Physiol 247:C240–C246

    CAS  PubMed  Google Scholar 

  58. Marcus DC, Liu J, Wangemann P (1994) Transepithelial voltage and resistance of vestibular dark cell epithelium from the gerbil ampulla. Hear Res 73:101–108

    CAS  PubMed  Google Scholar 

  59. Marcus DC, Marcus NY, Thalmann R (1981) Changes in cation contents of stria vascularis with ouabain and potassium-free perfusion. Hear Res 4:149–160

    CAS  PubMed  Google Scholar 

  60. Marcus DC, Rokugo M, Thalmann R (1985) Effects of barium and ion substitutions in artificial blood on endocochlear potential. Hear Res 17:79–86

    CAS  PubMed  Google Scholar 

  61. Marcus DC, Wu T, Wangemann P, Kofuji P (2002) KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential. Am J Physiol Cell Physiol 282:C403–C407

    CAS  PubMed  Google Scholar 

  62. Melichar I, Syka J (1977) Time course of anoxia-induced K+ concentration changes in the cochlea measured with K+ specific microelectrodes. Pflugers Arch 372:207–213

    CAS  PubMed  Google Scholar 

  63. Melichar I, Syka J (1987) Electrophysiological measurements of the stria vascularis potentials in vivo. Hear Res 25:35–43

    CAS  PubMed  Google Scholar 

  64. Minowa O, Ikeda K, Sugitani Y, Oshima T, Nakai S, Katori Y, Suzuki M, Furukawa M, Kawase T, Zheng Y, Ogura M, Asada Y, Watanabe K, Yamanaka H, Gotoh S, Nishi-Takeshima M, Sugimoto T, Kikuchi T, Takasaka T, Noda T (1999) Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness. Science 285:1408–1411

    CAS  PubMed  Google Scholar 

  65. Mori Y, Watanabe M, Inui T, Nimura Y, Araki M, Miyamoto M, Takenaka H, Kubota T (2009) Ca2+ regulation of endocochlear potential in marginal cells. J Physiol Sci 59:355–365

    CAS  PubMed  Google Scholar 

  66. Nagata K, Zheng L, Madathany T, Castiglioni AJ, Bartles JR, Garcia-Anoveros J (2008) The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration. Proc Natl Acad Sci U S A 105:353–358

    CAS  PubMed  Google Scholar 

  67. Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J, Faure S, Gary F, Coumel P, Petit C, Schwartz K, Guicheney P (1997) A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange–Nielsen cardioauditory syndrome. Nat Genet 15:186–189

    CAS  PubMed  Google Scholar 

  68. Nicolas M, Dememes D, Martin A, Kupershmidt S, Barhanin J (2001) KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells. Hear Res 153:132–145

    CAS  PubMed  Google Scholar 

  69. Nin F, Hibino H, Doi K, Suzuki T, Hisa Y, Kurachi Y (2008) The endocochlear potential depends on two K+ diffusion potentials and an electrical barrier in the stria vascularis of the inner ear. Proc Natl Acad Sci U S A 105:1751–1756

    CAS  PubMed  Google Scholar 

  70. Offner FF, Dallos P, Cheatham MA (1987) Positive endocochlear potential: mechanism of production by marginal cells of stria vascularis. Hear Res 29:117–124

    CAS  PubMed  Google Scholar 

  71. Oliver D, Klocker N, Schuck J, Baukrowitz T, Ruppersberg JP, Fakler B (2000) Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic transmission at auditory outer hair cells. Neuron 26:595–601

    CAS  PubMed  Google Scholar 

  72. Phippard D, Lu L, Lee D, Saunders JC, Crenshaw EB 3rd (1999) Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. J Neurosci 19:5980–5989

    CAS  PubMed  Google Scholar 

  73. Rickheit G, Maier H, Strenzke N, Andreescu CE, De Zeeuw CI, Muenscher A, Zdebik AA, Jentsch TJ (2008) Endocochlear potential depends on Cl− channels: mechanism underlying deafness in Bartter syndrome IV. EMBO J 27:2907–2917

    CAS  PubMed  Google Scholar 

  74. Rivas A, Francis HW (2005) Inner ear abnormalities in a Kcnq1 (Kvlqt1) knockout mouse: a model of Jervell and Lange–Nielsen syndrome. Otol Neurotol 26:415–424

    PubMed  Google Scholar 

  75. Ruttiger L, Sausbier M, Zimmermann U, Winter H, Braig C, Engel J, Knirsch M, Arntz C, Langer P, Hirt B, Muller M, Kopschall I, Pfister M, Munkner S, Rohbock K, Pfaff I, Rusch A, Ruth P, Knipper M (2004) Deletion of the Ca2+-activated potassium (BK) α-subunit but not the BKβ1-subunit leads to progressive hearing loss. Proc Natl Acad Sci U S A 101:12922–12927

    PubMed  Google Scholar 

  76. Sage CL, Marcus DC (2001) Immunolocalization of ClC-K chloride channel in strial marginal cells and vestibular dark cells. Hear Res 160:1–9

    CAS  PubMed  Google Scholar 

  77. Sakagami M, Fukazawa K, Matsunaga T, Fujita H, Mori N, Takumi T, Ohkubo H, Nakanishi S (1991) Cellular localization of rat Isk protein in the stria vascularis by immunohistochemical observation. Hear Res 56:168–172

    CAS  PubMed  Google Scholar 

  78. Sakaguchi N, Crouch JJ, Lytle C, Schulte BA (1998) Na-K-Cl cotransporter expression in the developing and senescent gerbil cochlea. Hear Res 118:114–122

    CAS  PubMed  Google Scholar 

  79. Salt AN, Melichar I, Thalmann R (1987) Mechanisms of endocochlear potential generation by stria vascularis. Laryngoscope 97:984–991

    CAS  PubMed  Google Scholar 

  80. Schlingmann KP, Konrad M, Jeck N, Waldegger P, Reinalter SC, Holder M, Seyberth HW, Waldegger S (2004) Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med 350:1314–1319

    CAS  PubMed  Google Scholar 

  81. Scholl UI, Choi M, Liu T, Ramaekers VT, Hausler MG, Grimmer J, Tobe SW, Farhi A, Nelson-Williams C, Lifton RP (2009) Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proc Natl Acad Sci U S A 106:5842–5847

    CAS  PubMed  Google Scholar 

  82. Schulte BA, Adams JC (1989) Distribution of immunoreactive Na+, K+-ATPase in gerbil cochlea. J Histochem Cytochem 37:127–134

    CAS  PubMed  Google Scholar 

  83. Schulte BA, Steel KP (1994) Expression of alpha and beta subunit isoforms of Na, K-ATPase in the mouse inner ear and changes with mutations at the Wv or Sld loci. Hear Res 78:65–76

    CAS  PubMed  Google Scholar 

  84. Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hordt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H (1997) KCNE1 mutations cause Jervell and Lange–Nielsen syndrome. Nat Genet 17:267–268

    CAS  PubMed  Google Scholar 

  85. Sellick PM, Johnstone BM (1972) The electrophysiology of the saccule. Pflugers Arch 336:28–34

    CAS  PubMed  Google Scholar 

  86. Shen Z, Marcus DC (1998) Divalent cations inhibit IsK/KvLQT1 channels in excised membrane patches of strial marginal cells. Hear Res 123:157–167

    CAS  PubMed  Google Scholar 

  87. Skinner LJ, Enee V, Beurg M, Jung HH, Ryan AF, Hafidi A, Aran JM, Dulon D (2003) Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea. J Neurophysiol 90:320–332

    CAS  PubMed  Google Scholar 

  88. Spicer SS, Schulte BA (1996) The fine structure of spiral ligament cells relates to ion return to the stria and varies with place-frequency. Hear Res 100:80–100

    CAS  PubMed  Google Scholar 

  89. Spicer SS, Schulte BA (2005) Novel structures in marginal and intermediate cells presumably relate to functions of apical versus basal strial strata. Hear Res 200:87–101

    PubMed  Google Scholar 

  90. Sterkers O, Saumon G, Tran Ba Huy P, Amiel C (1982) K, Cl, and H2O entry in endolymph, perilymph, and cerebrospinal fluid of the rat. Am J Physiol 243:F173–F180

    CAS  PubMed  Google Scholar 

  91. Sunose H, Ikeda K, Saito Y, Nishiyama A, Takasaka T (1993) Nonselective cation and Cl channels in luminal membrane of the marginal cell. Am J Physiol 265:C72–C78

    CAS  PubMed  Google Scholar 

  92. Sunose H, Ikeda K, Suzuki M, Takasaka T (1994) Voltage-activated K channel in luminal membrane of marginal cells of stria vascularis dissected from guinea pig. Hear Res 80:86–92

    CAS  PubMed  Google Scholar 

  93. Takeuchi S, Ando M (1998) Dye-coupling of melanocytes with endothelial cells and pericytes in the cochlea of gerbils. Cell Tissue Res 293:271–275

    CAS  PubMed  Google Scholar 

  94. Takeuchi S, Ando M (1998) Inwardly rectifying K+ currents in intermediate cells in the cochlea of gerbils: a possible contribution to the endocochlear potential. Neurosci Lett 247:175–178

    CAS  PubMed  Google Scholar 

  95. Takeuchi S, Ando M (1999) Voltage-dependent outward K+ current in intermediate cell of stria vascularis of gerbil cochlea. Am J Physiol 277:C91–C99

    CAS  PubMed  Google Scholar 

  96. Takeuchi S, Ando M, Kakigi A (2000) Mechanism generating endocochlear potential: role played by intermediate cells in stria vascularis. Biophys J 79:2572–2582

    CAS  PubMed  Google Scholar 

  97. Takeuchi S, Ando M, Kozakura K, Saito H, Irimajiri A (1995) Ion channels in basolateral membrane of marginal cells dissociated from gerbil stria vascularis. Hear Res 83:89–100

    CAS  PubMed  Google Scholar 

  98. Takeuchi S, Marcus DC, Wangemann P (1992) Ca2+-activated nonselective cation, maxi K+ and Cl− channels in apical membrane of marginal cells of stria vascularis. Hear Res 61:86–96

    CAS  PubMed  Google Scholar 

  99. Takumida M, Kubo N, Ohtani M, Suzuka Y, Anniko M (2005) Transient receptor potential channels in the inner ear: presence of transient receptor potential channel subfamily 1 and 4 in the guinea pig inner ear. Acta Otolaryngol 125:929–934

    PubMed  Google Scholar 

  100. Tasaki I, Spyropoulos CS (1959) Stria vascularis as source of endocochlear potential. J Neurophysiol 22:149–155

    CAS  PubMed  Google Scholar 

  101. ten Cate WJ, Curtis LM, Rarey KE (1994) Na, K-ATPase α and β subunit isoform distribution in the rat cochlear and vestibular tissues. Hear Res 75:151–160

    CAS  PubMed  Google Scholar 

  102. Teubner B, Michel V, Pesch J, Lautermann J, Cohen-Salmon M, Sohl G, Jahnke K, Winterhager E, Herberhold C, Hardelin JP, Petit C, Willecke K (2003) Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Hum Mol Genet 12:13–21

    CAS  PubMed  Google Scholar 

  103. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999) Jervell and Lange–Nielsen syndrome: a Norwegian perspective. Am J Med Genet 89:137–146

    CAS  PubMed  Google Scholar 

  104. Vetter DE, Mann JR, Wangemann P, Liu J, McLaughlin KJ, Lesage F, Marcus DC, Lazdunski M, Heinemann SF, Barhanin J (1996) Inner ear defects induced by null mutation of the isk gene. Neuron 17:1251–1264

    CAS  PubMed  Google Scholar 

  105. Vilstrup G (1955) The vitreous body and the endolymph as two related gelatinous substances; comparison of the two substances with reference to their hyaluronic acid and protein contents; preliminary report. Acta Ophthalmol (Copenh) 33:13–15

    CAS  Google Scholar 

  106. Vollrath MA, Kwan KY, Corey DP (2007) The micromachinery of mechanotransduction in hair cells. Annu Rev Neurosci 30:339–365

    CAS  PubMed  Google Scholar 

  107. Von Bekesy G (1952) DC resting potentials inside the cochlear partition. J Acoust Soc Amer 24:72–76

    Google Scholar 

  108. Von Bekesy G (1952) Resting potentials inside the cochlear partition of the guinea pig. Nature 169:241–242

    Google Scholar 

  109. Wada J, Kambayashi J, Marcus DC, Thalmann R (1979) Vascular perfusion of the cochlea: effect of potassium-free and rubidium-substituted media. Arch Otorhinolaryngol 225:79–81

    CAS  PubMed  Google Scholar 

  110. Wada J, Paloheimo S, Thalmann I, Bohne BA, Thalmann R (1979) Maintenance of cochlear function with artificial oxygen carriers. Laryngoscope 89:1457–1473

    CAS  PubMed  Google Scholar 

  111. Wang Q, Bowles NE, Towbin JA (1998) The molecular basis of long QT syndrome and prospects for therapy. Mol Med Today 4:382–388

    CAS  PubMed  Google Scholar 

  112. Wangemann P (1995) Comparison of ion transport mechanisms between vestibular dark cells and strial marginal cells. Hear Res 90:149–157

    CAS  PubMed  Google Scholar 

  113. Wangemann P (2002) K+ cycling and the endocochlear potential. Hear Res 165:1–9

    CAS  PubMed  Google Scholar 

  114. Wangemann P (2006) Supporting sensory transduction: cochlear fluid homeostasis and the endocochlear potential. J Physiol 576:11–21

    CAS  PubMed  Google Scholar 

  115. Wangemann P, Itza EM, Albrecht B, Wu T, Jabba SV, Maganti RJ, Lee JH, Everett LA, Wall SM, Royaux IE, Green ED, Marcus DC (2004) Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Med 2:30

    PubMed  Google Scholar 

  116. Wangemann P, Liu J, Marcus DC (1995) Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro. Hear Res 84:19–29

    CAS  PubMed  Google Scholar 

  117. Xu H, Delling M, Li L, Dong X, Clapham DE (2007) Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice. Proc Natl Acad Sci U S A 104:18321–18326

    CAS  PubMed  Google Scholar 

  118. Zidanic M, Brownell WE (1990) Fine structure of the intracochlear potential field. I. The silent current. Biophys J 57:1253–1268

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Bernd Nilius (KU Leuven) for providing us with an opportunity to write this review article and Dr. A. J. Hudspeth (The Rockefeller University) for his critical reading of the text. HH and YK are supported by the following research grants and funds: Grant-in-Aid for Scientific Research on Priority Areas 17081012 (to HH), Grant-in-Aid for Young Scientists (B) 19790188 (to HH), the Global COE Program “in silico medicine” at Osaka University (to HH, FN, and YK), and a grant for “Research and Development of Next-Generation Integrated Life Simulation Software” (to YK), from the Ministry of Education, Culture, Sport, Science and Technology of Japan, Senri Life Science Foundation (to HH), Japan Foundation for Applied Enzymology (to HH), and the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical care (to HH).

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  1. Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Hiroshi Hibino, Fumiaki Nin, Chizuru Tsuzuki & Yoshihisa Kurachi

  2. Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Fumiaki Nin

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  1. Hiroshi Hibino
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  2. Fumiaki Nin
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  4. Yoshihisa Kurachi
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Correspondence to Yoshihisa Kurachi.

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Hibino, H., Nin, F., Tsuzuki, C. et al. How is the highly positive endocochlear potential formed? The specific architecture of the stria vascularis and the roles of the ion-transport apparatus. Pflugers Arch - Eur J Physiol 459, 521–533 (2010). https://doi.org/10.1007/s00424-009-0754-z

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  • DOI: https://doi.org/10.1007/s00424-009-0754-z

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