Skip to main content
Log in

Potassium channels in pancreatic duct epithelial cells: their role, function and pathophysiological relevance

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

Abstract

Pancreatic ductal epithelial cells play a fundamental role in HCO3 secretion, a process which is essential for maintaining the integrity of the pancreas. Although several studies have implicated impaired HCO3 and fluid secretion as a triggering factor in the development of pancreatitis, the mechanism and regulation of HCO3 secretion is still not completely understood. To date, most studies on the ion transporters that orchestrate ductal HCO3 secretion have focussed on the role of Cl/HCO3 exchangers and Cl channels, whereas much less is known about the role of K+ channels. However, there is growing evidence that many types of K+ channels are present in ductal cells where they have an essential role in establishing and maintaining the electrochemical driving force for anion secretion. For this reason, strategies that increase K+ channel function may help to restore impaired HCO3 and fluid secretion, such as in pancreatitis, and therefore provide novel directions for future pancreatic therapy. In this review, our aims are to summarize the types of K+ channels found in pancreatic ductal cells and to discuss their individual roles in ductal HCO3 secretion. We will also describe how K+ channels are involved in pathophysiological conditions and discuss how they could act as new molecular targets for the development of therapeutic approaches to treat pancreatic diseases.

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

Similar content being viewed by others

References

  1. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97(2):175–187

    CAS  PubMed  Google Scholar 

  2. Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, Kurtz I (1998) Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. J Biol Chem 273(28):17689–17695

    CAS  PubMed  Google Scholar 

  3. Argent BE, Gray MA, Steward MC, Case RM (2012) Cell physiology of pancreatic ducts. In: Johnson LR (ed) Physiology of the gastrointestinal tract, vol 1, 5th edn. Academic Press, Oxford, pp 1399–1424

    Google Scholar 

  4. Barfield JP, Yeung CH, Cooper TG (2005) Characterization of potassium channels involved in volume regulation of human spermatozoa. Mol Hum Reprod 11(12):891–897

    CAS  PubMed  Google Scholar 

  5. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384(6604):78–80

    CAS  PubMed  Google Scholar 

  6. Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J, Poujeol P (2003) Role of TASK2 potassium channels regarding volume regulation in primary cultures of mouse proximal tubules. J Gen Physiol 122(2):177–190

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Behrendorff N, Floetenmeyer M, Schwiening C, Thorn P (2010) Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice. Gastroenterology 139(5):1711–1720, 1720 e1711–e1715

  8. Behrens R, Nolting A, Reimann F, Schwarz M, Waldschutz R, Pongs O (2000) hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. FEBS Lett 474(1):99–106

    CAS  PubMed  Google Scholar 

  9. Bentzen BH, Nardi A, Calloe K, Madsen LS, Olesen SP, Grunnet M (2007) The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels. Mol Pharmacol 72(4):1033–1044

    CAS  PubMed  Google Scholar 

  10. Bentzen BH, Osadchii O, Jespersen T, Hansen RS, Olesen SP, Grunnet M (2009) Activation of big conductance Ca(2+)-activated K(+) channels (BK) protects the heart against ischemia-reperfusion injury. Pflugers Arch 457(5):979–988

    CAS  PubMed  Google Scholar 

  11. Berridge MJ (1995) Calcium signalling and cell proliferation. Bioessays 17(6):491–500

    CAS  PubMed  Google Scholar 

  12. Bhattacharjee A, Joiner WJ, Wu M, Yang Y, Sigworth FJ, Kaczmarek LK (2003) Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J Neurosci 23(37):11681–11691

    CAS  PubMed  Google Scholar 

  13. Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS (2009) Reducing extracellular pH sensitizes the acinar cell to secretagogue-induced pancreatitis responses in rats. Gastroenterology 137(3):1083–1092

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Bielanska J, Hernandez-Losa J, Perez-Verdaguer M, Moline T, Somoza R, Ramon YCS, Condom E, Ferreres JC, Felipe A (2009) Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human cancer. Curr Cancer Drug Targets 9(8):904–914

    CAS  PubMed  Google Scholar 

  15. Bielanska J, Hernandez-Losa J, Moline T, Somoza R, Cajal SR, Condom E, Ferreres JC, Felipe A (2012) Increased voltage-dependent K(+) channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness. Oncol Lett 4(2):227–230

    PubMed Central  PubMed  Google Scholar 

  16. Blatz AL, Magleby KL (1986) Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle. Nature 323(6090):718–720

    CAS  PubMed  Google Scholar 

  17. Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J Biol Chem 275(9):6453–6461

    CAS  PubMed  Google Scholar 

  18. Camacho J (2006) Ether a go-go potassium channels and cancer. Cancer Lett 233(1):1–9

    CAS  PubMed  Google Scholar 

  19. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80(5):795–803

    CAS  PubMed  Google Scholar 

  20. D’Adamo MC, Shang L, Imbrici P, Brown SD, Pessia M, Tucker SJ (2011) Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity. J Biol Chem 286(1):192–198

    PubMed Central  PubMed  Google Scholar 

  21. Demolombe S, Franco D, de Boer P, Kuperschmidt S, Roden D, Pereon Y, Jarry A, Moorman AF, Escande D (2001) Differential expression of KvLQT1 and its regulator IsK in mouse epithelia. Am J Physiol Cell Physiol 280(2):C359–C372

    CAS  PubMed  Google Scholar 

  22. Derst C, Hirsch JR, Preisig-Muller R, Wischmeyer E, Karschin A, Doring F, Thomzig A, Veh RW, Schlatter E, Kummer W, Daut J (2001) Cellular localization of the potassium channel Kir7.1 in guinea pig and human kidney. Kidney Int 59:2197–2205

    CAS  PubMed  Google Scholar 

  23. Diener M, Hug F, Strabel D, Scharrer E (1996) Cyclic AMP-dependent regulation of K+ transport in the rat distal colon. Br J Pharmacol 118(6):1477–1487

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Dorwart MR, Shcheynikov N, Yang D, Muallem S (2008) The solute carrier 26 family of proteins in epithelial ion transport. Physiology (Bethesda) 23:104–114

    CAS  Google Scholar 

  25. Doupnik CA, Davidson N, Lester HA (1995) The inward rectifier potassium channel family. Curr Opin Neurobiol 5(3):268–277

    CAS  PubMed  Google Scholar 

  26. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 16(17):5464–5471

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Durie PR (1989) The pathophysiology of the pancreatic defect in cystic fibrosis. Acta Paediatr Scand Suppl 363:41–44

    CAS  PubMed  Google Scholar 

  28. Durie PR (1998) Pancreatitis and mutations of the cystic fibrosis gene. N Engl J Med 339(10):687–688

    CAS  PubMed  Google Scholar 

  29. Dutta AK, Khimji AK, Sathe M, Kresge C, Parameswara V, Esser V, Rockey DC, Feranchak AP (2009) Identification and functional characterization of the intermediate-conductance Ca(2+)-activated K(+) channel (IK-1) in biliary epithelium. Am J Physiol Gastrointest Liver Physiol 297(5):G1009–G1018

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J (1999) Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem 274(9):5746–5754

    CAS  PubMed  Google Scholar 

  31. Fedida D, Wible B, Wang Z, Fermini B, Faust F, Nattel S, Brown AM (1993) Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. Circ Res 73(1):210–216

    CAS  PubMed  Google Scholar 

  32. Flores CA, Melvin JE, Figueroa CD, Sepulveda FV (2007) Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4. J Physiol 583(Pt 2):705–717

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Fong P, Argent BE, Guggino WB, Gray MA (2003) Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF. Am J Physiol Cell Physiol 285(2):C433–C445

    CAS  PubMed  Google Scholar 

  34. Freedman SD, Kern HF, Scheele GA (2001) Pancreatic acinar cell dysfunction in CFTR(−/−) mice is associated with impairments in luminal pH and endocytosis. Gastroenterology 121(4):950–957

    CAS  PubMed  Google Scholar 

  35. Fuller CM, Eckhardt L, Schulz I (1989) Ionic and osmotic dependence of secretion from permeabilised acini of the rat pancreas. Pflugers Arch 413(4):385–394

    CAS  PubMed  Google Scholar 

  36. Furness JB, Robbins HL, Selmer IS, Hunne B, Chen MX, Hicks GA, Moore S, Neylon CB (2003) Expression of intermediate conductance potassium channel immunoreactivity in neurons and epithelial cells of the rat gastrointestinal tract. Cell Tissue Res 314(2):179–189

    CAS  PubMed  Google Scholar 

  37. Garcia-Calvo M, Knaus HG, McManus OB, Giangiacomo KM, Kaczorowski GJ, Garcia ML (1994) Purification and reconstitution of the high-conductance, calcium-activated potassium channel from tracheal smooth muscle. J Biol Chem 269(1):676–682

    CAS  PubMed  Google Scholar 

  38. Gardos G (1958) The function of calcium in the potassium permeability of human erythrocytes. Biochim Biophys Acta 30(3):653–654

    CAS  PubMed  Google Scholar 

  39. Girard C, Duprat F, Terrenoire C, Tinel N, Fosset M, Romey G, Lazdunski M, Lesage F (2001) Genomic and functional characteristics of novel human pancreatic 2p domain K+ channels. Biochem Biophys Res Commun 282:249–256

    CAS  PubMed  Google Scholar 

  40. Grady T, Mah’Moud M, Otani T, Rhee S, Lerch MM, Gorelick FS (1998) Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. Am J Physiol 275(5 Pt 1):G1010–G1017

    CAS  PubMed  Google Scholar 

  41. Gray MA, Greenwell JR, Garton AJ, Argent BE (1990) Regulation of maxi-K+ channels on pancreatic duct cells by cyclic AMP-dependent phosphorylation. J Membr Biol 115(3):203–215

    CAS  PubMed  Google Scholar 

  42. Greger R, Bleich M, Riedemann N, van Driessche W, Ecke D, Warth R (1997) The role of K+ channels in colonic Cl- secretion. Comp Biochem Physiol A Physiol 118(2):271–275

    CAS  PubMed  Google Scholar 

  43. Gukovsky I, Gukovskaya AS, Blinman TA, Zaninovic V, Pandol SJ (1998) Early NF-kappaB activation is associated with hormone-induced pancreatitis. Am J Physiol 275(6 Pt 1):G1402–G1414

    CAS  PubMed  Google Scholar 

  44. Hayashi M, Novak I (2013) Molecular basis of potassium channels in pancreatic duct epithelial cells. Channels (Austin) 7(6):432–441

    CAS  Google Scholar 

  45. Hayashi M, Wang J, Hede SE, Novak I (2012) An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells. Am J Physiol Cell Physiol 303(2):C151–C159

    CAS  PubMed  Google Scholar 

  46. Hede SE, Amstrup J, Klaerke DA, Novak I (2005) P2Y2 and P2Y4 receptors regulate pancreatic Ca(2+)-activated K+ channels differently. Pflugers Arch 450(6):429–436

    CAS  PubMed  Google Scholar 

  47. Hegyi P, Petersen OH (2013) The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology. Rev Physiol Biochem Pharmacol 165:1–30

    PubMed  Google Scholar 

  48. Hegyi P, Pandol S, Venglovecz V, Rakonczay Z Jr (2010) The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 60(4):544–552

    PubMed  Google Scholar 

  49. Hegyi P, Maleth J, Venglovecz V, Rakonczay Z Jr (2011) Pancreatic ductal bicarbonate secretion: challenge of the acinar Acid load. Front Physiol 2:36

    PubMed Central  PubMed  Google Scholar 

  50. Heitzmann D, Warth R (2008) Physiology and pathophysiology of potassium channels in gastrointestinal epithelia. Physiol Rev 88(3):1119–1182

    CAS  PubMed  Google Scholar 

  51. 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(1):76–84

    PubMed  Google Scholar 

  52. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90(1):291–366

    CAS  PubMed  Google Scholar 

  53. Hoffmann EK, Lambert IH, Pedersen SF (2009) Physiology of cell volume regulation in vertebrates. Physiol Rev 89(1):193–277

    CAS  PubMed  Google Scholar 

  54. Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, Seino Y, Mizuta M, Seino S (1995) Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem 270(11):5691–5694

    CAS  PubMed  Google Scholar 

  55. Isbrandt D, Leicher T, Waldschutz R, Zhu X, Luhmann U, Michel U, Sauter K, Pongs O (2000) Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Genomics 64(2):144–154

    CAS  PubMed  Google Scholar 

  56. Iwatsuki N, Petersen OH (1985) Inhibition of Ca2+-activated K+ channels in pig pancreatic acinar cells by Ba2+, Ca2+, quinine and quinidine. Biochim Biophys Acta 819(2):249–257

    CAS  PubMed  Google Scholar 

  57. Jager H, Dreker T, Buck A, Giehl K, Gress T, Grissmer S (2004) Blockage of intermediate-conductance Ca2+-activated K+ channels inhibit human pancreatic cancer cell growth in vitro. Mol Pharmacol 65(3):630–638

    PubMed  Google Scholar 

  58. Jan LY, Jan YN (1997) Cloned potassium channels from eukaryotes and prokaryotes. Annu Rev Neurosci 20:91–123

    CAS  PubMed  Google Scholar 

  59. Jehle J, Schweizer PA, Katus HA, Thomas D (2011) Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis 2(8):e193

    PubMed Central  CAS  PubMed  Google Scholar 

  60. Jensen BS, Strobaek D, Christophersen P, Jorgensen TD, Hansen C, Silahtaroglu A, Olesen SP, Ahring PK (1998) Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel. Am J Physiol 275(3 Pt 1):C848–C856

    CAS  PubMed  Google Scholar 

  61. Jensen BS, Odum N, Jorgensen NK, Christophersen P, Olesen SP (1999) Inhibition of T cell proliferation by selective block of Ca(2+)-activated K(+) channels. Proc Natl Acad Sci U S A 96(19):10917–10921

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Joiner WJ, Basavappa S, Vidyasagar S, Nehrke K, Krishnan S, Binder HJ, Boulpaep EL, Rajendran VM (2003) Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon. Am J Physiol Gastrointest Liver Physiol 285(1):G185–G196

    CAS  PubMed  Google Scholar 

  63. Ju M, Wray D (2002) Molecular identification and characterisation of the human EAG2 potassium channel. FEBS Lett 524(1–3):204–210

    CAS  PubMed  Google Scholar 

  64. Judak L, Hegyi P, Rakonczay Z Jr, Maleth J, Gray MA, Venglovecz V (2014) Ethanol and its non-oxidative metabolites profoundly inhibit CFTR function in pancreatic epithelial cells which is prevented by ATP supplementation. Pflugers Arch 466(3):549–562

    CAS  PubMed  Google Scholar 

  65. Jung SR, Kim K, Hille B, Nguyen TD, Koh DS (2006) Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells. J Physiol 576(Pt 1):163–178

    PubMed Central  CAS  PubMed  Google Scholar 

  66. Kaczmarek LK (2013) Slack, Slick and sodium-activated potassium channels. ISRN Neurosci 2013 (2013)

  67. Kalman K, Nguyen A, Tseng-Crank J, Dukes ID, Chandy G, Hustad CM, Copeland NG, Jenkins NA, Mohrenweiser H, Brandriff B, Cahalan M, Gutman GA, Chandy KG (1998) Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7. J Biol Chem 273(10):5851–5857

    CAS  PubMed  Google Scholar 

  68. Kang D, Kim D (2004) Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem Biophys Res Commun 315(4):836–844

    CAS  PubMed  Google Scholar 

  69. Kelly ML, Abu-Hamdah R, Jeremic A, Cho SJ, Ilie AE, Jena BP (2005) Patch clamped single pancreatic zymogen granules: direct measurements of ion channel activities at the granule membrane. Pancreatology 5(4–5):443–449

    CAS  PubMed  Google Scholar 

  70. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245(4922):1073–1080

    CAS  PubMed  Google Scholar 

  71. Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA (1995) A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature 376(6542):690–695

    CAS  PubMed  Google Scholar 

  72. Khanna R, Chang MC, Joiner WJ, Kaczmarek LK, Schlichter LC (1999) hSK4/hIK1, a calmodulin-binding KCa channel in human T lymphocytes. Roles in proliferation and volume regulation. J Biol Chem 274(21):14838–14849

    CAS  PubMed  Google Scholar 

  73. Kiehn J, Lacerda AE, Wible B, Brown AM (1996) Molecular physiology and pharmacology of HERG. Single-channel currents and block by dofetilide. Circulation 94(10):2572–2579

    CAS  PubMed  Google Scholar 

  74. Kim D, Gnatenco C (2001) TASK-5, a new member of the tandem-pore K(+) channel family. Biochem Biophys Res Commun 284(4):923–930

    CAS  PubMed  Google Scholar 

  75. Kim SJ, Greger R (1999) Voltage-dependent, slowly activating K+ current (I(Ks)) and its augmentation by carbachol in rat pancreatic acini. Pflugers Arch 438(5):604–611

    CAS  PubMed  Google Scholar 

  76. Kim SJ, Kerst G, Schreiber R, Pavenstadt H, Greger R, Hug MJ, Bleich M (2000) Inwardly rectifying K+ channels in the basolateral membrane of rat pancreatic acini. Pflugers Arch 441(2–3):331–340

    CAS  PubMed  Google Scholar 

  77. Knaus HG, Garcia-Calvo M, Kaczorowski GJ, Garcia ML (1994) Subunit composition of the high conductance calcium-activated potassium channel from smooth muscle, a representative of the mSlo and slowpoke family of potassium channels. J Biol Chem 269(6):3921–3924

    CAS  PubMed  Google Scholar 

  78. Kondo C, Isomoto S, Matsumoto S, Yamamda M, Horio Y, Yamashita S, Takemura-Kameda K, Matsuzawa Y, Kurachi Y (1996) Cloning and functional expression of a novel isoform of ROMK inwardly rectifying ATP-dependent K+ channel, ROMK6 (Kir1.1f). FEBS Lett 399:122–126

    CAS  PubMed  Google Scholar 

  79. Lachheb S, Cluzeaud F, Bens M, Genete M, Hibino H, Lourdel S, Kurachi Y, Vandewalle A, Teulon J, Paulais M (2008) Kir4.1/Kir5.1 channel forms the major K+ channel in the basolateral membrane of mouse renal collecting duct principal cells. Am J Physiol Renal Physiol 294(6):F1398–F1407

    CAS  PubMed  Google Scholar 

  80. Lansu K, Gentile S (2013) Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program. Cell Death Dis 4:e652

    PubMed Central  CAS  PubMed  Google Scholar 

  81. Latorre R, Oberhauser A, Labarca P, Alvarez O (1989) Varieties of calcium-activated potassium channels. Annu Rev Physiol 51:385–399

    CAS  PubMed  Google Scholar 

  82. Lee MP, Ravenel JD, Hu RJ, Lustig LR, Tomaselli G, Berger RD, Brandenburg SA, Litzi TJ, Bunton TE, Limb C, Francis H, Gorelikow M, Gu H, Washington K, Argani P, Goldenring JR, Coffey RJ, Feinberg AP (2000) Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice. J Clin Invest 106(12):1447–1455

    PubMed Central  CAS  PubMed  Google Scholar 

  83. Lee MG, Ohana E, Park HW, Yang D, Muallem S (2012) Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion. Physiol Rev 92(1):39–74

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Liu Y, Holmgren M, Jurman ME, Yellen G (1997) Gated access to the pore of a voltage-dependent K+ channel. Neuron 19(1):175–184

    PubMed  Google Scholar 

  85. Liu Y, McKenna E, Figueroa DJ, Blevins R, Austin CP, Bennett PB, Swanson R (2000) The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas. Cytogenet Cell Genet 90(1–2):60–63

    CAS  PubMed  Google Scholar 

  86. Lohrmann E, Burhoff I, Nitschke RB, Lang HJ, Mania D, Englert HC, Hropot M, Warth R, Rohm W, Bleich M et al (1995) A new class of inhibitors of cAMP-mediated Cl- secretion in rabbit colon, acting by the reduction of cAMP-activated K+ conductance. Pflugers Arch 429(4):517–530

    CAS  PubMed  Google Scholar 

  87. Long SB, Campbell EB, Mackinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309(5736):897–903

    CAS  PubMed  Google Scholar 

  88. Long SB, Campbell EB, Mackinnon R (2005) Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309(5736):903–908

    CAS  PubMed  Google Scholar 

  89. Loussouarn G, Demolombe S, Mohammad-Panah R, Escande D, Baro I (1996) Expression of CFTR controls cAMP-dependent activation of epithelial K+ currents. Am J Physiol 271(5 Pt 1):C1565–C1573

    CAS  PubMed  Google Scholar 

  90. MacDonald PE, Ha XF, Wang J, Smukler SR, Sun AM, Gaisano HY, Salapatek AM, Backx PH, Wheeler MB (2001) Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol Endocrinol 15(8):1423–1435

    CAS  PubMed  Google Scholar 

  91. Madden ME, Sarras MP Jr (1987) Distribution of Na+, K+-ATPase in rat exocrine pancreas as monitored by K+-NPPase cytochemistry and [3H]-ouabain binding: a plasma membrane protein found primarily to be ductal cell associated. J Histochem Cytochem 35(12):1365–1374

    CAS  PubMed  Google Scholar 

  92. Maleth J, Hegyi P (2014) Calcium signaling in pancreatic ductal epithelial cells: an old friend and a nasty enemy. Cell Calcium

  93. Maleth J, Venglovecz V, Razga Z, Tiszlavicz L, Rakonczay Z Jr, Hegyi P (2011) Non-conjugated chenodeoxycholate induces severe mitochondrial damage and inhibits bicarbonate transport in pancreatic duct cells. Gut 60(1):136–138

    CAS  PubMed  Google Scholar 

  94. Maleth J, Rakonczay Z Jr, Venglovecz V, Dolman NJ, Hegyi P (2013) Central role of mitochondrial injury in the pathogenesis of acute pancreatitis. Acta Physiol (Oxf) 207(2):226–235

    CAS  Google Scholar 

  95. Mannuzzu LM, Moronne MM, Isacoff EY (1996) Direct physical measure of conformational rearrangement underlying potassium channel gating. Science 271(5246):213–216

    CAS  PubMed  Google Scholar 

  96. Manzanares D, Gonzalez C, Ivonnet P, Chen RS, Valencia-Gattas M, Conner GE, Larsson HP, Salathe M (2011) Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume. J Biol Chem 286(22):19830–19839

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Marty A (1981) Ca-dependent K channels with large unitary conductance in chromaffin cell membranes. Nature 291(5815):497–500

    CAS  PubMed  Google Scholar 

  98. Marty A, Tan YP, Trautmann A (1984) Three types of calcium-dependent channel in rat lacrimal glands. J Physiol 357:293–325

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Maruyama Y, Petersen OH, Flanagan P, Pearson GT (1983) Quantification of Ca2+-activated K+ channels under hormonal control in pig pancreas acinar cells. Nature 305(5931):228–232

    CAS  PubMed  Google Scholar 

  100. McManus OB, Helms LM, Pallanck L, Ganetzky B, Swanson R, Leonard RJ (1995) Functional role of the beta subunit of high conductance calcium-activated potassium channels. Neuron 14(3):645–650

    CAS  PubMed  Google Scholar 

  101. Medhurst AD, Rennie G, Chapman CG, Meadows H, Duckworth MD, Kelsell RE, Gloger II, Pangalos MN (2001) Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Brain Res Mol Brain Res 86(1–2):101–114

    CAS  PubMed  Google Scholar 

  102. Meera P, Wallner M, Song M, Toro L (1997) Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc Natl Acad Sci U S A 94(25):14066–14071

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Miller C (2000) An overview of the potassium channel family. Genome Biol 1(4):reviews0004.1–0004.5

  104. Morton MJ, O’Connell AD, Sivaprasadarao A, Hunter M (2003) Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and −2. Pflugers Arch 445(5):577–583

    CAS  PubMed  Google Scholar 

  105. Nakamoto T, Romanenko VG, Takahashi A, Begenisich T, Melvin JE (2008) Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland. Am J Physiol Cell Physiol 294(3):C810–C819

    PubMed Central  CAS  PubMed  Google Scholar 

  106. Nanda Kumar NS, Singh SK, Rajendran VM (2010) Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon. Am J Physiol Gastrointest Liver Physiol 299(3):G707–G714

    PubMed Central  CAS  PubMed  Google Scholar 

  107. Nehrke K, Quinn CC, Begenisich T (2003) Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol 284(2):C535–C546

    CAS  PubMed  Google Scholar 

  108. Nelson MT, Cheng H, Rubart M, Santana LF, Bonev AD, Knot HJ, Lederer WJ (1995) Relaxation of arterial smooth muscle by calcium sparks. Science 270(5236):633–637

    CAS  PubMed  Google Scholar 

  109. Nguyen TD, Moody MW (1998) Calcium-activated potassium conductances on cultured nontransformed dog pancreatic duct epithelial cells. Pancreas 17(4):348–358

    CAS  PubMed  Google Scholar 

  110. Niemeyer MI, Cid LP, Barros LF, Sepulveda FV (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem 276(46):43166–43174

    CAS  PubMed  Google Scholar 

  111. Niemeyer MI, Gonzalez-Nilo FD, Zuniga L, Gonzalez W, Cid LP, Sepulveda FV (2006) Gating of two-pore domain K+ channels by extracellular pH. Biochem Soc Trans 34(Pt 5):899–902

    CAS  PubMed  Google Scholar 

  112. Niemeyer MI, Cid LP, Pena-Munzenmayer G, Sepulveda FV (2010) Separate gating mechanisms mediate the regulation of K2P potassium channel TASK-2 by intra- and extracellular pH. J Biol Chem 285(22):16467–16475

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Novak I, Greger R (1988) Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane. Pflugers Arch 411(1):58–68

    CAS  PubMed  Google Scholar 

  114. Novak I, Greger R (1991) Effect of bicarbonate on potassium conductance of isolated perfused rat pancreatic ducts. Pflugers Arch 419(1):76–83

    CAS  PubMed  Google Scholar 

  115. Okolo C, Wong T, Moody MW, Nguyen TD (2002) Effects of bile acids on dog pancreatic duct epithelial cell secretion and monolayer resistance. Am J Physiol Gastrointest Liver Physiol 283(5):G1042–G1050

    CAS  PubMed  Google Scholar 

  116. Opie E (1901) The etiology of acute haemorrhagic pancreatitis. Johns Hopkins Hosp Bull 12:182–188

    Google Scholar 

  117. Orio P, Rojas P, Ferreira G, Latorre R (2002) New disguises for an old channel: MaxiK channel beta-subunits. News Physiol Sci 17:156–161

    CAS  PubMed  Google Scholar 

  118. Oshiro T, Takahashi H, Ohsaga A, Ebihara S, Sasaki H, Maruyama Y (2005) Delayed expression of large conductance K+ channels reshaping agonist-induced currents in mouse pancreatic acinar cells. J Physiol 563(Pt 2):379–391

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ (2002) Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome. Proc Natl Acad Sci U S A 99(12):7986–7991

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Pallagi P, Venglovecz V, Rakonczay Z Jr., Borka K, Korompay A, Ozsvari B, Judak L, Sahin-Toth M, Geisz A, Schnur A, Maleth J, Takacs T, Gray MA, Argent BE, Mayerle J, Lerch MM, Wittmann T, Hegyi P (2011) Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl(−) channels and luminal anion exchangers. Gastroenterology 141(6):2228–2239 e2226. doi:10.1053/j.gastro.2011.08.039

  121. Pallagi P, Balla Z, Singh AK, Dosa S, Ivanyi B, Kukor Z, Toth A, Riederer B, Liu Y, Engelhardt R, Jarmay K, Szabo A, Janovszky A, Perides G, Venglovecz V, Maleth J, Wittmann T, Takacs T, Gray MA, Gacser A, Hegyi P, Seidler U, Rakonczay Z Jr (2014) The role of pancreatic ductal secretion in protection against acute pancreatitis in mice*. Crit Care Med 42(3):e177–e188

    CAS  PubMed  Google Scholar 

  122. Papazian DM, Shao XM, Seoh SA, Mock AF, Huang Y, Wainstock DH (1995) Electrostatic interactions of S4 voltage sensor in Shaker K+ channel. Neuron 14(6):1293–1301

    CAS  PubMed  Google Scholar 

  123. Pardo LA, Stuhmer W (2014) The roles of K(+) channels in cancer. Nat Rev Cancer 14(1):39–48

    CAS  PubMed  Google Scholar 

  124. Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S, Stuhmer W (1999) Oncogenic potential of EAG K(+) channels. Embo J 18(20):5540–5547

    PubMed Central  CAS  PubMed  Google Scholar 

  125. Park KP, Beck JS, Douglas IJ, Brown PD (1994) Ca(2+)-activated K+ channels are involved in regulatory volume decrease in acinar cells isolated from the rat lacrimal gland. J Membr Biol 141(2):193–201

    CAS  PubMed  Google Scholar 

  126. Park HW, Nam JH, Kim JY, Namkung W, Yoon JS, Lee JS, Kim KS, Venglovecz V, Gray MA, Kim KH, Lee MG (2012) Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139(2):620–631

    Google Scholar 

  127. Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S (2013) Irbit mediates synergy between Ca(2+) and cAMP signaling pathways during epithelial transport in mice. Gastroenterology 145(1):232–241

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Pedersen SF, Hoffmann EK, Novak I (2013) Cell volume regulation in epithelial physiology and cancer. Front Physiol 4:233

    PubMed Central  PubMed  Google Scholar 

  129. Perozo E, Santacruz-Toloza L, Stefani E, Bezanilla F, Papazian DM (1994) S4 mutations alter gating currents of Shaker K channels. Biophys J 66(2 Pt 1):345–354

    PubMed Central  CAS  PubMed  Google Scholar 

  130. Petersen OH, Ueda N (1975) Pancreatic acinar cells: effect of acetylcholine, pancreozymin, gastrin and secretin on membrane potential and resistance in vivo and in vitro. J Physiol 247(2):461–471

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Petersen OH, Findlay I, Iwatsuki N, Singh J, Gallacher DV, Fuller CM, Pearson GT, Dunne MJ, Morris AP (1985) Human pancreatic acinar cells: studies of stimulus-secretion coupling. Gastroenterology 89(1):109–117

    CAS  PubMed  Google Scholar 

  132. Pluznick JL, Sansom SC (2006) BK channels in the kidney: role in K(+) secretion and localization of molecular components. Am J Physiol Renal Physiol 291(3):F517–F529

    CAS  PubMed  Google Scholar 

  133. Quinton PM (2008) Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet 372(9636):415–417

    CAS  PubMed  Google Scholar 

  134. Reber HA, Mosley JG (1980) The effect of bile salts on the pancreatic duct mucosal barrier. Br J Surg 67(1):59–62

    CAS  PubMed  Google Scholar 

  135. Reber HA, Roberts C, Way LW (1979) The pancreatic duct mucosal barrier. Am J Surg 137(1):128–134

    CAS  PubMed  Google Scholar 

  136. Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem 273(47):30863–30869

    CAS  PubMed  Google Scholar 

  137. Robitaille R, Garcia ML, Kaczorowski GJ, Charlton MP (1993) Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release. Neuron 11(4):645–655

    CAS  PubMed  Google Scholar 

  138. Saganich MJ, Vega-Saenz de Miera E, Nadal MS, Baker H, Coetzee WA, Rudy B (1999) Cloning of components of a novel subthreshold-activating K(+) channel with a unique pattern of expression in the cerebral cortex. J Neurosci 19(24):10789–10802

    CAS  PubMed  Google Scholar 

  139. Sah P (1996) Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci 19(4):150–154

    CAS  PubMed  Google Scholar 

  140. Sakmann B, Trube G (1984) Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol 347:641–657

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Saluja AK, Bhagat L, Lee HS, Bhatia M, Frossard JL, Steer ML (1999) Secretagogue-induced digestive enzyme activation and cell injury in rat pancreatic acini. Am J Physiol 276(4 Pt 1):G835–G842

    CAS  PubMed  Google Scholar 

  142. Saluja AK, Lerch MM, Phillips PA, Dudeja V (2007) Why does pancreatic overstimulation cause pancreatitis? Annu Rev Physiol 69:249–269

    CAS  PubMed  Google Scholar 

  143. Sanguinetti MC, Tristani-Firouzi M (2006) hERG potassium channels and cardiac arrhythmia. Nature 440(7083):463–469

    CAS  PubMed  Google Scholar 

  144. Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81(2):299–307

    CAS  PubMed  Google Scholar 

  145. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT (1996) Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 384(6604):80–83

    CAS  PubMed  Google Scholar 

  146. Santi CM, Ferreira G, Yang B, Gazula VR, Butler A, Wei A, Kaczmarek LK, Salkoff L (2006) Opposite regulation of Slick and Slack K+ channels by neuromodulators. J Neurosci 26(19):5059–5068

    CAS  PubMed  Google Scholar 

  147. Sausbier M, Matos JE, Sausbier U, Beranek G, Arntz C, Neuhuber W, Ruth P, Leipziger J (2006) Distal colonic K(+) secretion occurs via BK channels. J Am Soc Nephrol 17(5):1275–1282

    CAS  PubMed  Google Scholar 

  148. Scheele GA, Fukuoka SI, Kern HF, Freedman SD (1996) Pancreatic dysfunction in cystic fibrosis occurs as a result of impairments in luminal pH, apical trafficking of zymogen granule membranes, and solubilization of secretory enzymes. Pancreas 12(1):1–9

    CAS  PubMed  Google Scholar 

  149. Schroeder BC, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch TJ (2000) A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature 403(6766):196–199

    CAS  PubMed  Google Scholar 

  150. Sewell WA, Young JA (1975) Secretion of electrolytes by the pancreas of the anaestetized rat. J Physiol 252(2):379–396

    PubMed Central  CAS  PubMed  Google Scholar 

  151. Shcheynikov N, Wang Y, Park M, Ko SB, Dorwart M, Naruse S, Thomas PJ, Muallem S (2006) Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6. J Gen Physiol 127(5):511–524

    PubMed Central  CAS  PubMed  Google Scholar 

  152. Shieh CC, Klemic KG, Kirsch GE (1997) Role of transmembrane segment S5 on gating of voltage-dependent K+ channels. J Gen Physiol 109(6):767–778

    PubMed Central  CAS  PubMed  Google Scholar 

  153. Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52(4):557–594

    CAS  PubMed  Google Scholar 

  154. Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, Bienkowski MJ (1997) Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir12 and Kir13). J Biol Chem 272:586–593

    CAS  PubMed  Google Scholar 

  155. Skryma RN, Prevarskaya NB, Dufy-Barbe L, Odessa MF, Audin J, Dufy B (1997) Potassium conductance in the androgen-sensitive prostate cancer cell line, LNCaP: involvement in cell proliferation. Prostate 33(2):112–122

    CAS  PubMed  Google Scholar 

  156. Skryma R, Van Coppenolle F, Dufy-Barbe L, Dufy B, Prevarskaya N (1999) Characterization of Ca(2+)-inhibited potassium channels in the LNCaP human prostate cancer cell line. Recept Channels 6(4):241–253

    CAS  PubMed  Google Scholar 

  157. Smith PL, Baukrowitz T, Yellen G (1996) The inward rectification mechanism of the HERG cardiac potassium channel. Nature 379(6568):833–836

    CAS  PubMed  Google Scholar 

  158. Song P, Groos S, Riederer B, Feng Z, Krabbenhoft A, Smolka A, Seidler U (2009) KCNQ1 is the luminal K+ recycling channel during stimulation of gastric acid secretion. J Physiol 587(Pt 15):3955–3965

    PubMed Central  CAS  PubMed  Google Scholar 

  159. Sorensen MV, Matos JE, Praetorius HA, Leipziger J (2010) Colonic potassium handling. Pflugers Arch 459(5):645–656

    CAS  PubMed  Google Scholar 

  160. Spitzner M, Ousingsawat J, Scheidt K, Kunzelmann K, Schreiber R (2007) Voltage-gated K+ channels support proliferation of colonic carcinoma cells. FASEB J 21(1):35–44

    CAS  PubMed  Google Scholar 

  161. Steward MC, Ishiguro H, Case RM (2005) Mechanisms of bicarbonate secretion in the pancreatic duct. Annu Rev Physiol 67:377–409

    CAS  PubMed  Google Scholar 

  162. Stewart AK, Yamamoto A, Nakakuki M, Kondo T, Alper SL, Ishiguro H (2009) Functional coupling of apical Cl/HCO3− exchange with CFTR in stimulated HCO3- secretion by guinea pig interlobular pancreatic duct. Am J Physiol Gastrointest Liver Physiol 296(6):G1307–G1317

    PubMed Central  CAS  PubMed  Google Scholar 

  163. Stuenkel EL, Machen TE, Williams JA (1988) pH regulatory mechanisms in rat pancreatic ductal cells. Am J Physiol 254(6 Pt 1):G925–G930

    CAS  PubMed  Google Scholar 

  164. Su K, Kyaw H, Fan P, Zeng Z, Shell BK, Carter KC, Li Y (1997) Isolation, characterization, and mapping of two human potassium channels. Biochem Biophys Res Commun 241(3):675–681

    CAS  PubMed  Google Scholar 

  165. Suzuki K, Petersen OH (1988) Patch-clamp study of single-channel and whole-cell K+ currents in guinea pig pancreatic acinar cells. Am J Physiol 255(3 Pt 1):G275–G285

    CAS  PubMed  Google Scholar 

  166. Takacs T, Rosztoczy A, Maleth J, Rakonczay Z Jr, Hegyi P (2013) Intraductal acidosis in acute biliary pancreatitis. Pancreatology 13(4):333–335

    PubMed  Google Scholar 

  167. Takahata T, Hayashi M, Ishikawa T (2003) SK4/IK1-like channels mediate TEA-insensitive, Ca2+-activated K+ currents in bovine parotid acinar cells. Am J Physiol Cell Physiol 284(1):C127–C144

    CAS  PubMed  Google Scholar 

  168. Takumi T, Ohkubo H, Nakanishi S (1988) Cloning of a membrane protein that induces a slow voltage-gated potassium current. Science 242(4881):1042–1045

    CAS  PubMed  Google Scholar 

  169. Tamarina NA, Wang Y, Mariotto L, Kuznetsov A, Bond C, Adelman J, Philipson LH (2003) Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Diabetes 52(8):2000–2006

    CAS  PubMed  Google Scholar 

  170. Tanemoto M, Kittaka N, Inanobe A, Kurachi Y (2000) In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1. J Physiol 525(Pt 3):587–592

    PubMed Central  CAS  PubMed  Google Scholar 

  171. Tarasov A, Dusonchet J, Ashcroft F (2004) Metabolic regulation of the pancreatic beta-cell ATP-sensitive K+ channel: a pas de deux. Diabetes 53(Suppl 3):S113–S122

    CAS  PubMed  Google Scholar 

  172. Thevenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283(3):C651–C672

    CAS  PubMed  Google Scholar 

  173. Thompson-Vest N, Shimizu Y, Hunne B, Furness JB (2006) The distribution of intermediate-conductance, calcium-activated, potassium (IK) channels in epithelial cells. J Anat 208(2):219–229

    PubMed Central  CAS  PubMed  Google Scholar 

  174. Toro L, Wallner M, Meera P, Tanaka Y (1998) Maxi-K(Ca), a unique member of the voltage-gated K channel superfamily. News Physiol Sci 13:112–117

    CAS  PubMed  Google Scholar 

  175. Trapani JG, Korn SJ (2003) Effect of external pH on activation of the Kv1.5 potassium channel. Biophys J 84(1):195–204

    PubMed Central  CAS  PubMed  Google Scholar 

  176. Tucker SJ, Imbrici P, Salvatore L, D’Adamo MC, Pessia M (2000) pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia. J Biol Chem 275(22):16404–16407

    CAS  PubMed  Google Scholar 

  177. Valverde MA, O’Brien JA, Sepulveda FV, Ratcliff RA, Evans MJ, Colledge WH (1995) Impaired cell volume regulation in intestinal crypt epithelia of cystic fibrosis mice. Proc Natl Acad Sci U S A 92(20):9038–9041

    PubMed Central  CAS  PubMed  Google Scholar 

  178. vanTol BL, Missan S, Crack J, Moser S, Baldridge WH, Linsdell P, Cowley EA (2007) Contribution of KCNQ1 to the regulatory volume decrease in the human mammary epithelial cell line MCF-7. Am J Physiol Cell Physiol 293(3):C1010–C1019

    CAS  PubMed  Google Scholar 

  179. Vaughn J, Wolford JK, Prochazka M, Permana PA (2000) Genomic structure and expression of human KCNJ9 (Kir3.3/GIRK3). Biochem Biophys Res Commun 274(2):302–309

    CAS  PubMed  Google Scholar 

  180. Venglovecz V, Rakonczay Z Jr, Ozsvari B, Takacs T, Lonovics J, Varro A, Gray MA, Argent BE, Hegyi P (2008) Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig. Gut 57(8):1102–1112

    CAS  PubMed  Google Scholar 

  181. Venglovecz V, Hegyi P, Rakonczay Z Jr, Tiszlavicz L, Nardi A, Grunnet M, Gray MA (2011) Pathophysiological relevance of apical large-conductance Ca(2)+-activated potassium channels in pancreatic duct epithelial cells. Gut 60(3):361–369

    CAS  PubMed  Google Scholar 

  182. Vergara C, Latorre R, Marrion NV, Adelman JP (1998) Calcium-activated potassium channels. Curr Opin Neurobiol 8(3):321–329

    CAS  PubMed  Google Scholar 

  183. Villalonga N, Martinez-Marmol R, Roura-Ferrer M, David M, Valenzuela C, Soler C, Felipe A (2008) Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation. Biochim Biophys Acta 1783(5):728–736

    CAS  PubMed  Google Scholar 

  184. Villanger O, Veel T, Raeder MG (1995) Secretin causes H+/HCO3− secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase. Gastroenterology 108(3):850–859

    CAS  PubMed  Google Scholar 

  185. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Toubin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 12(1):17–23

    PubMed  Google Scholar 

  186. Wang Y, Soyombo AA, Shcheynikov N, Zeng W, Dorwart M, Marino CR, Thomas PJ, Muallem S (2006) Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3− secretion: relevance to cystic fibrosis. Embo J 25(21):5049–5057

    PubMed Central  CAS  PubMed  Google Scholar 

  187. Wang J, Haanes KA, Novak I (2013) Purinergic regulation of CFTR and Ca(2+)-activated Cl(−) channels and K(+) channels in human pancreatic duct epithelium. Am J Physiol Cell Physiol 304(7):C673–C684

    CAS  PubMed  Google Scholar 

  188. Warmke JW, Ganetzky B (1994) A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A 91(8):3438–3442

    PubMed Central  CAS  PubMed  Google Scholar 

  189. Warth R, Bleich M (2000) K+ channels and colonic function. Rev Physiol Biochem Pharmacol 140:1–62

    CAS  PubMed  Google Scholar 

  190. Warth R, Hamm K, Bleich M, Kunzelmann K, von Hahn T, Schreiber R, Ullrich E, Mengel M, Trautmann N, Kindle P, Schwab A, Greger R (1999) Molecular and functional characterization of the small Ca(2+)-regulated K+ channel (rSK4) of colonic crypts. Pflugers Arch 438(4):437–444

    CAS  PubMed  Google Scholar 

  191. Warth R, Garcia Alzamora M, Kim JK, Zdebik A, Nitschke R, Bleich M, Gerlach U, Barhanin J, Kim SJ (2002) The role of KCNQ1/KCNE1 K(+) channels in intestine and pancreas: lessons from the KCNE1 knockout mouse. Pflugers Arch 443(5–6):822–828

    CAS  PubMed  Google Scholar 

  192. Warth R, Barriere H, Meneton P, Bloch M, Thomas J, Tauc M, Heitzmann D, Romeo E, Verrey F, Mengual R, Guy N, Bendahhou S, Lesage F, Poujeol P, Barhanin J (2004) Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proc Natl Acad Sci U S A 101(21):8215–8220

    PubMed Central  CAS  PubMed  Google Scholar 

  193. Woodfork KA, Wonderlin WF, Peterson VA, Strobl JS (1995) Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture. J Cell Physiol 162(2):163–171

    CAS  PubMed  Google Scholar 

  194. Yan L, Figueroa DJ, Austin CP, Liu Y, Bugianesi RM, Slaughter RS, Kaczorowski GJ, Kohler MG (2004) Expression of voltage-gated potassium channels in human and rhesus pancreatic islets. Diabetes 53(3):597–607

    CAS  PubMed  Google Scholar 

  195. Yang Y, Sigworth FJ (1998) Single-channel properties of IKs potassium channels. J Gen Physiol 112(6):665–678

    PubMed Central  CAS  PubMed  Google Scholar 

  196. Yang WP, Levesque PC, Little WA, Conder ML, Shalaby FY, Blanar MA (1997) KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias. Proc Natl Acad Sci U S A 94(8):4017–4021

    PubMed Central  CAS  PubMed  Google Scholar 

  197. Yao X, Forte JG (2003) Cell biology of acid secretion by the parietal cell. Annu Rev Physiol 65:103–131

    CAS  PubMed  Google Scholar 

  198. Yazejian B, DiGregorio DA, Vergara JL, Poage RE, Meriney SD, Grinnell AD (1997) Direct measurements of presynaptic calcium and calcium-activated potassium currents regulating neurotransmitter release at cultured Xenopus nerve-muscle synapses. J Neurosci 17(9):2990–3001

    CAS  PubMed  Google Scholar 

  199. Yeung CH, Cooper TG (2008) Potassium channels involved in human sperm volume regulation–quantitative studies at the protein and mRNA levels. Mol Reprod Dev 75(4):659–668

    CAS  PubMed  Google Scholar 

  200. Yoshimoto Y, Fukuyama Y, Horio Y, Inanobe A, Gotoh M, Kurachi Y (1999) Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K+ channel. FEBS Lett 444(2–3):265–269

    CAS  PubMed  Google Scholar 

  201. Yuan A, Santi CM, Wei A, Wang ZW, Pollak K, Nonet M, Kaczmarek L, Crowder CM, Salkoff L (2003) The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron 37(5):765–773

    CAS  PubMed  Google Scholar 

  202. Zhao KQ, Xiong G, Wilber M, Cohen NA, Kreindler JL (2012) A role for two-pore K(+) channels in modulating Na(+) absorption and Cl(−) secretion in normal human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 302(1):L4–L12

    PubMed Central  CAS  PubMed  Google Scholar 

  203. Zhou J, Jeron A, London B, Han X, Koren G (1998) Characterization of a slowly inactivating outward current in adult mouse ventricular myocytes. Circ Res 83(8):806–814

    CAS  PubMed  Google Scholar 

  204. Zhu XR, Wulf A, Schwarz M, Isbrandt D, Pongs O (1999) Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Recept Channels 6(5):387–400

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Our research is supported by Hungarian National Development Agency grants (TÁMOP-4.2.2.A-11/1/KONV-2012-0035, TÁMOP-4.2.2-A-11/1/KONV-2012-0052, TÁMOP-4.2.2.A-11/1/KONV-2012-0073), the Hungarian Scientific Research Fund (OTKA NF105758, NF100677, K109756) and the Hungarian Academy of Sciences (BO/00531/11/5). This research was also supported by the European Union and the State of Hungary, cofinanced by the European Social Fund in the framework of TÁMOP 4.2.4.A/2-11-1-2012-0001 ‘National Excellence Program’ and MTA-SZTE Momentum Grant (LP2014-10/2014).

Conflict of interest

The authors hereby declare that there is no conflict of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Viktória Venglovecz or Péter Hegyi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Venglovecz, V., Rakonczay, Z., Gray, M.A. et al. Potassium channels in pancreatic duct epithelial cells: their role, function and pathophysiological relevance. Pflugers Arch - Eur J Physiol 467, 625–640 (2015). https://doi.org/10.1007/s00424-014-1585-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-014-1585-0

Keywords

Navigation