Skip to main content

Heartburn: cardiac potassium channels involved in parietal cell acid secretion

Abstract

Hydrochloric acid is produced in parietal cells of the gastric glands by an H+/K+-ATPase. This proton pump couples the outwards movement of H+ to the inwards movement of K+ thus requiring the presence of luminal K+ to operate. To maintain the activity of the pump, K+ recirculates over the apical membrane via conductive pathways, the molecular nature of which has been identified in the past few years. This review gives a short overview about the recent advances in the understanding of the role of K+ channels in the process of parietal cell H+ secretion and focuses on the identification of KCNQ1/KCNE2 K+ channel as the molecular correlate of the parietal cell apical potassium conductance.

This is a preview of subscription content, access via your institution.

Fig. 1.

References

  1. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) KvLQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384:78–80

    Google Scholar 

  2. Busch AE, Busch GL, Ford E, Suessbrich H, Lang HJ, Greger R, Kunzelmann K, Attali B, Stuhmer W (1997) The role of the IsK protein in the specific pharmacological properties of the IKs channel complex. Br J Pharmacol 122:187–189

    CAS  PubMed  Google Scholar 

  3. Dedek K, Waldegger S (2001) Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract. Pflugers Arch 442:896–902

    Article  CAS  PubMed  Google Scholar 

  4. Franic TV, Judd LM, Robinson D, Barrett SP, Scarff KL, Gleeson PA, Samuelson LC, Van Driel IR (2001) Regulation of gastric epithelial cell development revealed in H+/K+-ATPase beta-subunit- and gastrin-deficient mice. Am J Physiol 281:G1502–G1511

    CAS  Google Scholar 

  5. Freeman LC, Lippold JJ, Mitchell KE (2000) Glycosylation influences gating and pH sensitivity of I(sK). J Membr Biol 177:65–79

    Article  CAS  PubMed  Google Scholar 

  6. Fujita A, Horio Y, Higashi K, Mouri T, Hata F, Takeguchi N, Kurachi Y (2002) Specific localization of an inwardly rectifying K+ channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its possible involvement in K+ recycling for the H+-K+-pump. J Physiol (Lond) 540:85–92

    Google Scholar 

  7. Grahammer F, Herling AW, Lang HJ, Schmitt-Graff A, Wittekindt OH, Nitschke R, Bleich M, Barhanin J, Warth R (2001) The cardiac K+ channel KCNQ1 is essential for gastric acid secretion. Gastroenterology 120:1363–1371

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Higashi K, Fujita A, Inanobe A, Tanemoto M, Doi K, Kubo T, Kurachi Y (2001) An inwardly rectifying K+ channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain. Am J Physiol 281:C922–C931

    CAS  Google Scholar 

  10. Ishii M, Horio Y, Tada Y, Hibino H, Inanobe A, Ito M, Yamada M, Gotow T, Uchiyama Y, Kurachi Y (1997) Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Muller cell membrane: their regulation by insulin and laminin signals. J Neurosci 17:7725–7735

    CAS  PubMed  Google Scholar 

  11. Ito M, Inanobe A, Horio Y, Hibino H, Isomoto S, Ito H, Mori K, Tonosaki A, Tomoike H, Kurachi Y (1996) Immunolocalization of an inwardly rectifying K+ channel, K(AB)-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia. FEBS Lett 388:11–15

    Article  CAS  PubMed  Google Scholar 

  12. Jentsch TJ (2000) Neuronal KCNQ potassium channels: physiology and role in disease. Nat Rev Neurosci 1:21–30

    Article  CAS  PubMed  Google Scholar 

  13. Kotera T, Hashimoto A, Ueda S, Okada Y (1991) Whole-cell K+ current activation in response to voltages and carbachol in gastric parietal cells isolated from guinea pig. J Membr Biol 124:43–52

    CAS  PubMed  Google Scholar 

  14. 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 

  15. Lauf PK, Adragna NC (2000) K-Cl cotransport: properties and molecular mechanism. Cell Physiol Biochem 10:341–354

    CAS  PubMed  Google Scholar 

  16. 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 106:1447–1455

    CAS  PubMed  Google Scholar 

  17. Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K (2000) Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J Biol Chem 275:22395–22400

    CAS  PubMed  Google Scholar 

  18. Lock H, Valverde MA (2000) Contribution of the IsK (MinK) potassium channel subunit to regulatory volume decrease in murine tracheal epithelial cells. J Biol Chem 275:34849–34852

    CAS  PubMed  Google Scholar 

  19. MacVinish LJ, Hickman ME, Mufti DA, Durrington HJ, Cuthbert AW (1998) Importance of basolateral K+ conductance in maintaining Cl secretion in murine nasal and colonic epithelia. J Physiol (Lond) 510:237–247

    Google Scholar 

  20. Melman YF, Krummerman A, McDonald TV (2002) KCNE regulation of KvLQT1 channels: structure-function correlates. Trends Cardiovasc Med 12:182–187

    Article  CAS  PubMed  Google Scholar 

  21. Mieno H, Kajiyama G (1991) Electrical characteristics of inward-rectifying K+ channels in isolated bullfrog oxyntic cells. Am J Physiol 261:G206–G212

    CAS  PubMed  Google Scholar 

  22. Munson K, Lambrecht N, Shin JM, Sachs G (2000) Analysis of the membrane domain of the gastric H+/K+-ATPase. J Exp Biol 203:161–170

    CAS  PubMed  Google Scholar 

  23. Nichols CG, Lopatin AN (1997) Inward rectifier potassium channels. Annu Rev Physiol 59:171–191

    CAS  PubMed  Google Scholar 

  24. Reenstra WW, Forte JG (1990) Characterization of K+ and Cl conductances in apical membrane vesicles from stimulated rabbit oxyntic cells. Am J Physiol 259:G850–G858

    CAS  PubMed  Google Scholar 

  25. Reimann F, Ashcroft FM (1999) Inwardly rectifying potassium channels. Curr Opin Cell Biol 11:503–508

    Article  CAS  PubMed  Google Scholar 

  26. Robbins J (2001) KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 90:1–19

    Article  CAS  PubMed  Google Scholar 

  27. Sakai H, Okada Y, Morii M, Takeguchi N (1989) Anion and cation channels in the basolateral membrane of rabbit parietal cells. Pflugers Arch 414:185–192

    CAS  PubMed  Google Scholar 

  28. Sandle GI, Fraser G, Fogg K, Warhurst G (1993) Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites. Gut 34:1331–1338

    CAS  PubMed  Google Scholar 

  29. Sanguinetti MC (2000) Maximal function of minimal K+ channel subunits. Trends Pharmacol Sci 21:199–201

    Article  CAS  PubMed  Google Scholar 

  30. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT (1996) Coassembly of KvLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel. Nature 384:80–83

    Google Scholar 

  31. Scarff KL, Judd LM, Toh BH, Gleeson PA, Van Driel IR (1999) Gastric H+,K+-adenosine triphosphatase beta subunit is required for normal function, development, and membrane structure of mouse parietal cells. Gastroenterology 117:605–618

    CAS  PubMed  Google Scholar 

  32. Schroeder BC, Kubisch C, Stein V, Jentsch TJ (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 396:687–690

    Article  CAS  PubMed  Google Scholar 

  33. Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ (2000) KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem 275:24089–24095

    CAS  PubMed  Google Scholar 

  34. 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 403:196–199

    CAS  PubMed  Google Scholar 

  35. Sheng M, Sala C (2001) PDZ domains and the organization of supramolecular complexes. Annu Rev Neurosci 24:1–29

    Article  CAS  PubMed  Google Scholar 

  36. Suessbrich H, Bleich M, Ecke D, Rizzo M, Waldegger S, Lang F, Szabo I, Lang HJ, Kunzelmann K, Greger R, Busch AE (1996) Specific blockade of slowly activating IsK channels by chromanols—impact on the role of I(sK) channels in epithelia. FEBS Lett 396:271–275

    CAS  PubMed  Google Scholar 

  37. Supplisson S, Loo DD, Sachs G (1991) Diversity of K+ channels in the basolateral membrane of resting Necturus oxyntic cells. J Membr Biol 123:209–221

    CAS  PubMed  Google Scholar 

  38. Supplisson S, Loo DD, Sachs G (1993) Whole-cell currents in isolated resting Necturus gastric oxynticopeptic cells. J Physiol (Lond) 463:57–82

    Google Scholar 

  39. Tinel N, Diochot S, Borsotto M, Lazdunski M, Barhanin J (2000) KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. EMBO J 19:6326–6330

    Google Scholar 

  40. Van Driel IR, Callaghan JM (1995) Proton and potassium transport by H+/K+-ATPases. Clin Exp Pharmacol Physiol 22:952–960

    PubMed  Google Scholar 

  41. 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 12:17–23

    PubMed  Google Scholar 

  42. Wolosin JM, Forte JG (1984) Stimulation of oxyntic cell triggers K+ and Cl conductances in apical H+-K+-ATPase membrane. Am J Physiol 246:C537–C545

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The financial support by the DFG (WA 1088/3-1), the Kempkes foundation and Aventis is acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Siegfried Waldegger.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Waldegger, S. Heartburn: cardiac potassium channels involved in parietal cell acid secretion. Pflugers Arch - Eur J Physiol 446, 143–147 (2003). https://doi.org/10.1007/s00424-003-1048-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1048-5

Keywords

  • KCNQ1
  • KCNE2
  • Proton pump
  • Potassium recirculation
  • Epithelial potassium channel