Digestive Diseases and Sciences

, Volume 50, Issue 11, pp 2043–2049 | Cite as

Cell Volume Regulation During Hyperosmotic Shrinkage Is Mediated by Na+/K+-ATPase and Na+–K+–2Cl Cotransporter in Necturus Gastrics Surface Epithelial Cells

  • Outi Nylander-Koski
  • Harri Mustonen
  • Tuula Kiviluoto
  • Eero Kivilaakso


Cell volume regulation was investigated in gastric surface epithelial cells during hypertonic conditions. Isolated Necturus antral mucosa was perfused on the serosal side with Ringer's solution (pH 7.25, 95%O2/5%CO2) and on the mucosal side successively with 150–500 mM NaCl. Amiloride, ouabain, and bumetanide were used to experimentally inhibit Na+/H+, Na+/K+ ATPase or Na+–K+–2Cl ion transporters. Intracellular sodium activity and cell volume changes were measured with liquid sensor microelectrodes. The increase in intracellular sodium activity caused by luminal hyperosmolar exposure was mainly due to cell shrinkage. Inhibition of Na+/K+ ATPase or Na+–K+–2Cl cotransporter increased hyperosmotic cell shrinkage (−52 ± 5%, −85 ± 19%, and −77 ± 9% for control, ouabain, and bumetanide, respectively). Inhibition of Na+/K+ ATPase increased intracellular sodium activity (from 18 ± 4 to 52 ± 12 mM). Cell volume regulation in gastric epithelial surface cells during mucosal hyperosmolar exposure is maintained by the basolateral Na+–K+–2Cl cotransporter, while Na+/K+ ATPase maintains sodium balance, but Na+/H+ antiport seems to have a less important role.


cell volume regulation gastric mucosa microelectrodes Na+/K+ ATPase Na+–K+–2Cl cotransporter Na+/H+ exchanger 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wills NK, Reuss L, Lewis SA, Karin NJ, Zang MIN, Decker ER, O'Neill R: Epithelial Transport. London, Chapman & Hall, 1996Google Scholar
  2. 2.
    O'Neill WC: Physiological significance of volume-regulatory transporters. Am J Physiol 276:C995–C1011, 1999PubMedGoogle Scholar
  3. 3.
    Jin NG, Kim JK, Yang DK, Cho SJ, Kim JM, Koh EJ, Jung HC, So I, Kim KW: Fundamental role of ClC3 in volume-sensitive Cl-channel function and cell volume regulation in AGS cells. Am J Physiol Gastrointest Liver Physiol 285:G938–G948, 2003PubMedGoogle Scholar
  4. 4.
    Mustonen H, Kivilaakso E: Effect of luminal ethanol on epithelial resistances and cell volume in isolated Necturus gastric mucosa. Dig Dis Sci 48:2037–2044, 2003CrossRefPubMedGoogle Scholar
  5. 5.
    Mustonen H, Kiviluoto T, Puolakkainen P, Kivilaakso E: Ethanol induces volume changes and gap junction closure via intracellular Ca2+ signalling pathway in cultured rabbit gastric epithelial cells. Scand J Gastroenterol 39:104–110, 2004CrossRefPubMedGoogle Scholar
  6. 6.
    Mustonen H, Kiviluoto T, Paimela H, Puolakkainen P, Kivilaakso E: Calcium signaling is involved in ethanol induced volume decrease and gap junction closure in cultured rat gastric mucosal cells. Dig Dis Sci 50:103–110, 2005CrossRefPubMedGoogle Scholar
  7. 7.
    Mustonen H, Kivilaakso E: Luminal acid increases apical cell membrane resistance in isolated Necturus antral mucosa. Gastroenterology 113:875–883, 1997PubMedGoogle Scholar
  8. 8.
    Reuss L: Changes in cell volume measured with an electrophysiologic technique. Proc Natl Acad Sci USA 82:6014–6018, 1985PubMedGoogle Scholar
  9. 9.
    Adorante JS: Regulatory volume decrease in frog retinal pigment epithelium. Am J Physiol 268:C89–C100, 1995PubMedGoogle Scholar
  10. 10.
    Kivilaakso E, Kiviluoto T: Intracellular pH in isolated Necturus antral mucosa in simulated ulcerogenic conditions. Gastroenterology 95:1198–1205, 1988PubMedGoogle Scholar
  11. 11.
    Kiviluoto T, Mustonen H, Salo J, Kivilaakso E: Regulation of intracellular pH in isolated Necturus gastric mucosa during short-term exposure to luminal acid. Gastroenterology 108:999–1004, 1995CrossRefPubMedGoogle Scholar
  12. 12.
    Hoffmann EK, Dunham PB: Membrane mechanisms and intracellular signalling in cell volume regulation. Int Rev Cytol 161:173–262, 1995PubMedGoogle Scholar
  13. 13.
    Xu J, Barone S, Petrovic S, Wang Z, Seidler U, Riederer B, Ramaswamy K, Dudeja PK, Shull GE, Soleimani M: Identification of an apical Cl/HCO3 exchanger in gastric surface mucous and duodenal villus cells. Am J Physiol Gastrointest Liver Physiol 285:G1225–G1234, 2003PubMedGoogle Scholar
  14. 14.
    Rossmann H, Bachmann O, Vieillard-Baron D, Gregor M, Seidler U: Na+/HCO3 cotransport and expression of NBC1 and NBC2 in rabbit gastric parietal and mucous cells. Gastroenterology 116:1389–1398, 1999PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Outi Nylander-Koski
    • 1
  • Harri Mustonen
    • 1
  • Tuula Kiviluoto
    • 1
  • Eero Kivilaakso
    • 1
  1. 1.Department of SurgeryHelsinki University Central HospitalHelsinkiFinland

Personalised recommendations