Skip to main content
PMC home page
Gut logoLink to Gut
. 1993 Oct;34(10):1331–1338. doi: 10.1136/gut.34.10.1331

Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites.

G I Sandle 1, G Fraser 1, K Fogg 1, G Warhurst 1
PMCID: PMC1374536  PMID: 8244097

Abstract

The HGT-1 human gastric cell line is similar to acid secreting parietal cells in that it possesses H2 receptors, histamine sensitive adenyl cyclase, and Cl- channels, which are activated by histamine by a cyclic adenosine monophosphate (cAMP) dependent mechanism. To discover if HGT-1 cells have additional properties found in parietal cells, [3H]omeprazole and patch clamp recording techniques were used to evaluate specific omeprazole binding sites and K+ channels in the plasma membrane. HGT-1 cells exhibited [3H]omeprazole binding in the non-stimulated state, which increased 100% in the presence of 1 mM histamine. High conductance (about 155 pS) K+ channels were active spontaneously in 17% of cell attached or excised inside out patches in non-stimulated subconfluent HGT-1 cells. In inside out patches, channel activity increased fivefold during depolarisation, ion substitution experiments confirmed that the channels were highly selective for K+, and channel activity was almost abolished by removal of Ca2+ or addition of 5 mM Ba2+. In quiescent cell attached patches, 0.1 mM dibutyryl cAMP failed to activate K+ channels. In contrast, 6.7 microM A23187 (a Ca2+ ionophore) increased intracellular Ca2+ concentration from mean (SEM) 14 (3) nM to 248 (30) nM and activated K+ channels in 21% of patches. It is concluded that the plasma membrane of HGT-1 cells possesses (a) specific 3H-omeprazole binding sites, which may reflect the omeprazole sensitive H+,K(+)-ATPase present in gastric parietal cells; and (b) Ca(2+)-activated K+ channels, which may be located in the basolateral membrane of human gastric parietal cells and play a part in acid secretion triggered by Ca(2+)-mediated secretory agonists.

Full text

PDF
1336

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVIS T. L., RUTLEDGE J. R., KEESEE D. C., BAJANDAS F. J., REHM W. S. ACID SECRETION, POTENTIAL, AND RESISTANCE OF FROG STOMACH IN K+-FREE SOLUTIONS. Am J Physiol. 1965 Jul;209:146–152. doi: 10.1152/ajplegacy.1965.209.1.146. [DOI] [PubMed] [Google Scholar]
  2. Cheret A. M., Laboisse C. L., Roumagnac I., Augeron C., Lewin M. J. Highly histamine-responsive clones from the human gastric adenocarcinoma cell line HGT-1. Agents Actions. 1986 Mar;17(5-6):436–440. doi: 10.1007/BF01965510. [DOI] [PubMed] [Google Scholar]
  3. Chew C. S., Brown M. R. Histamine increases phosphorylation of 27- and 40-kDa parietal cell proteins. Am J Physiol. 1987 Dec;253(6 Pt 1):G823–G829. doi: 10.1152/ajpgi.1987.253.6.G823. [DOI] [PubMed] [Google Scholar]
  4. Chew C. S., Hersey S. J., Sachs G., Berglindh T. Histamine responsiveness of isolated gastric glands. Am J Physiol. 1980 Apr;238(4):G312–G320. doi: 10.1152/ajpgi.1980.238.4.G312. [DOI] [PubMed] [Google Scholar]
  5. Cuppoletti J., Sachs G. Regulation of gastric acid secretion via modulation of a chloride conductance. J Biol Chem. 1984 Dec 10;259(23):14952–14959. [PubMed] [Google Scholar]
  6. Debellis L., Curci S., Frömter E. Effect of histamine on the basolateral K+ conductance of frog stomach oxyntic cells and surface epithelial cells. Am J Physiol. 1990 Apr;258(4 Pt 1):G631–G636. doi: 10.1152/ajpgi.1990.258.4.G631. [DOI] [PubMed] [Google Scholar]
  7. Demarest J. R., Machen T. E. Microelectrode measurements from oxyntic cells in intact Necturus gastric mucosa. Am J Physiol. 1985 Nov;249(5 Pt 1):C535–C540. doi: 10.1152/ajpcell.1985.249.5.C535. [DOI] [PubMed] [Google Scholar]
  8. Fellenius E., Berglindh T., Sachs G., Olbe L., Elander B., Sjöstrand S. E., Wallmark B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature. 1981 Mar 12;290(5802):159–161. doi: 10.1038/290159a0. [DOI] [PubMed] [Google Scholar]
  9. Forte J. G., Lee H. C. Gastric adenosine triphosphatases: a review of their possible role in HCl secretion. Gastroenterology. 1977 Oct;73(4 Pt 2):921–926. [PubMed] [Google Scholar]
  10. Forte T. M., Machen T. E., Forte J. G. Ultrastructural and physiological changes in piglet oxyntic cells during histamine stimulation and metabolic inhibition. Gastroenterology. 1975 Dec;69(6):1208–1222. [PubMed] [Google Scholar]
  11. Ganser A. L., Forte J. G. K + -stimulated ATPase in purified microsomes of bullfrog oxyntic cells. Biochim Biophys Acta. 1973 Apr 25;307(1):169–180. doi: 10.1016/0005-2736(73)90035-7. [DOI] [PubMed] [Google Scholar]
  12. Giebisch G., Hunter M., Kawahara K. Apical potassium channels in Amphiuma diluting segment: effect of barium. J Physiol. 1990 Jan;420:313–323. doi: 10.1113/jphysiol.1990.sp017914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldman D. E. POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES. J Gen Physiol. 1943 Sep 20;27(1):37–60. doi: 10.1085/jgp.27.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  15. Gögelein H., Greger R., Schlatter E. Potassium channels in the basolateral membrane of the rectal gland of Squalus acanthias. Regulation and inhibitors. Pflugers Arch. 1987 Jun;409(1-2):107–113. doi: 10.1007/BF00584756. [DOI] [PubMed] [Google Scholar]
  16. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  18. Ito S., Schofield G. C. Studies on the depletion and accumulation of microvilli and changes in the tubulovesicular compartment of mouse parietal cells in relation to gastric acid secretion. J Cell Biol. 1974 Nov;63(2 Pt 1):364–382. doi: 10.1083/jcb.63.2.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koelz H. R., Sachs G., Berglindh T. Cation effects on acid secretion in rabbit gastric glands. Am J Physiol. 1981 Nov;241(5):G431–G442. doi: 10.1152/ajpgi.1981.241.5.G431. [DOI] [PubMed] [Google Scholar]
  20. Kunzelmann K., Pavenstädt H., Greger R. Characterization of potassium channels in respiratory cells. II. Inhibitors and regulation. Pflugers Arch. 1989 Jul;414(3):297–303. doi: 10.1007/BF00584630. [DOI] [PubMed] [Google Scholar]
  21. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  22. Laboisse C. L., Augeron C., Couturier-Turpin M. H., Gespach C., Cheret A. M., Potet F. Characterization of a newly established human gastric cancer cell line HGT-1 bearing histamine H2-receptors. Cancer Res. 1982 Apr;42(4):1541–1548. [PubMed] [Google Scholar]
  23. Malinowska D. H. Cl- channel blockers inhibit acid secretion in rabbit parietal cells. Am J Physiol. 1990 Oct;259(4 Pt 1):G536–G543. doi: 10.1152/ajpgi.1990.259.4.G536. [DOI] [PubMed] [Google Scholar]
  24. Mieno H., Kajiyama G. Electrical characteristics of inward-rectifying K+ channels in isolated bullfrog oxyntic cells. Am J Physiol. 1991 Aug;261(2 Pt 1):G206–G212. doi: 10.1152/ajpgi.1991.261.2.G206. [DOI] [PubMed] [Google Scholar]
  25. Morris A. P., Gallacher D. V., Lee J. A. A large conductance, voltage- and calcium-activated K+ channel in the basolateral membrane of rat enterocytes. FEBS Lett. 1986 Sep 29;206(1):87–92. doi: 10.1016/0014-5793(86)81346-1. [DOI] [PubMed] [Google Scholar]
  26. Negulescu P. A., Machen T. E. Intracellular Ca regulation during secretagogue stimulation of the parietal cell. Am J Physiol. 1988 Jan;254(1 Pt 1):C130–C140. doi: 10.1152/ajpcell.1988.254.1.C130. [DOI] [PubMed] [Google Scholar]
  27. Perez A., Blissard D., Sachs G., Hersey S. J. Evidence for a chloride conductance in secretory membrane of parietal cells. Am J Physiol. 1989 Feb;256(2 Pt 1):G299–G305. doi: 10.1152/ajpgi.1989.256.2.G299. [DOI] [PubMed] [Google Scholar]
  28. Rehm W. S., Sanders S. S., Rutledge J. R., Davis T. L., Kurfees J. F., Keesee D. C., Bajandas F. J. Effect of removal of external K+ on frog's stomach in Cl-minus-free solutions. Am J Physiol. 1966 Apr;210(4):689–693. doi: 10.1152/ajplegacy.1966.210.4.689. [DOI] [PubMed] [Google Scholar]
  29. Sachs G., Chang H. H., Rabon E., Schackman R., Lewin M., Saccomani G. A nonelectrogenic H+ pump in plasma membranes of hog stomach. J Biol Chem. 1976 Dec 10;251(23):7690–7698. [PubMed] [Google Scholar]
  30. Sakai H., Okada Y., Morii M., Takeguchi N. Anion and cation channels in the basolateral membrane of rabbit parietal cells. Pflugers Arch. 1989 Jun;414(2):185–192. doi: 10.1007/BF00580962. [DOI] [PubMed] [Google Scholar]
  31. Sanders S. S., Noyes D. H., Spangler S. G., Rehm W. S. Demonstration of a barium-potassium antagonism on lumen side of in vitro frog stomach. Am J Physiol. 1973 Jun;224(6):1254–1259. doi: 10.1152/ajplegacy.1973.224.6.1254. [DOI] [PubMed] [Google Scholar]
  32. Sandle G. I., Fraser G., Long S., Warhurst G. A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1). Pflugers Arch. 1990 Nov;417(3):259–263. doi: 10.1007/BF00370990. [DOI] [PubMed] [Google Scholar]
  33. Schettino T., Köhler M., Frömter E. Membrane potentials of individual cells of isolated gastric glands of rabbit. Pflugers Arch. 1985 Sep;405(1):58–65. doi: 10.1007/BF00591098. [DOI] [PubMed] [Google Scholar]
  34. Schettino T., Trischitta F. Transport properties of the basolateral membrane of the oxyntic cells in frog fundic gastric mucosa. Pflugers Arch. 1989 Aug;414(4):469–476. doi: 10.1007/BF00585059. [DOI] [PubMed] [Google Scholar]
  35. Soll A. H. Potentiating interactions of gastric stimulants on [14 C] aminopyrine accumulation by isolated canine parietal cells. Gastroenterology. 1982 Jul;83(1 Pt 2):216–223. [PubMed] [Google Scholar]
  36. Ueda S., Loo D. D., Sachs G. Regulation of K+ channels in the basolateral membrane of Necturus oxyntic cells. J Membr Biol. 1987;97(1):31–41. doi: 10.1007/BF01869612. [DOI] [PubMed] [Google Scholar]
  37. Vergara C., Latorre R. Kinetics of Ca2+-activated K+ channels from rabbit muscle incorporated into planar bilayers. Evidence for a Ca2+ and Ba2+ blockade. J Gen Physiol. 1983 Oct;82(4):543–568. doi: 10.1085/jgp.82.4.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wolosin J. M., Forte J. G. Kinetic properties of the KCl transport at the secreting apical membrane of the oxyntic cell. J Membr Biol. 1983;71(3):195–207. doi: 10.1007/BF01875461. [DOI] [PubMed] [Google Scholar]
  39. Wolosin J. M., Forte J. G. Stimulation of oxyntic cell triggers K+ and Cl- conductances in apical H+-K+-ATPase membrane. Am J Physiol. 1984 May;246(5 Pt 1):C537–C545. doi: 10.1152/ajpcell.1984.246.5.C537. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES