Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jun 15;88(12):5277–5281. doi: 10.1073/pnas.88.12.5277

Cystic fibrosis gene expression is not correlated with rectifying Cl- channels.

C L Ward 1, M E Krouse 1, D C Gruenert 1, R R Kopito 1, J J Wine 1
PMCID: PMC51855  PMID: 1711224

Abstract

Cystic fibrosis (CF) involves a profound reduction of Cl- permeability in several exocrine tissues. A distinctive, outwardly rectifying, depolarization-induced Cl- channel (ORDIC channel) has been proposed to account for the Cl- conductance that is defective in CF. The recently identified CF gene is predicted to code for a 1480-amino acid integral membrane protein termed the CF transmembrane conductance regulator (CFTR). The CFTR shares sequence similarity with a superfamily of ATP-binding membrane transport proteins such as P-glycoprotein and STE6, but it also has features consistent with an ion channel function. It has been proposed that the CFTR might be an ORDIC channel. To determine if CFTR and ORDIC channel expression are correlated, we surveyed various cell lines for natural variation in CFTR and ORDIC channel expression. In four human epithelial cell lines (T84, CaCo2, PANC-1, and 9HTEo-/S) that encompass the full observed range of CFTR mRNA levels and ORDIC channel density we found no correlation.

Full text

PDF
5277

Images in this article

5279Image
on p.5279
5279Image
on p.5279
5279Image
on p.5279
5280Image
on p.5280
5280Image
on p.5280
5280Image
on p.5280

Selected References

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

  1. Barres B. A., Chun L. L., Corey D. P. Ion channel expression by white matter glia: I. Type 2 astrocytes and oligodendrocytes. Glia. 1988;1(1):10–30. doi: 10.1002/glia.440010104. [DOI] [PubMed] [Google Scholar]
  2. Bear C. E. Phosphorylation-activated chloride channels in human skin fibroblasts. FEBS Lett. 1988 Sep 12;237(1-2):145–149. doi: 10.1016/0014-5793(88)80189-3. [DOI] [PubMed] [Google Scholar]
  3. Chelly J., Concordet J. P., Kaplan J. C., Kahn A. Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2617–2621. doi: 10.1073/pnas.86.8.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen J. H., Schulman H., Gardner P. A cAMP-regulated chloride channel in lymphocytes that is affected in cystic fibrosis. Science. 1989 Feb 3;243(4891):657–660. doi: 10.1126/science.2464852. [DOI] [PubMed] [Google Scholar]
  5. Cliff W. H., Frizzell R. A. Separate Cl- conductances activated by cAMP and Ca2+ in Cl(-)-secreting epithelial cells. Proc Natl Acad Sci U S A. 1990 Jul;87(13):4956–4960. doi: 10.1073/pnas.87.13.4956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drumm M. L., Pope H. A., Cliff W. H., Rommens J. M., Marvin S. A., Tsui L. C., Collins F. S., Frizzell R. A., Wilson J. M. Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell. 1990 Sep 21;62(6):1227–1233. doi: 10.1016/0092-8674(90)90398-x. [DOI] [PubMed] [Google Scholar]
  7. Frizzell R. A., Rechkemmer G., Shoemaker R. L. Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science. 1986 Aug 1;233(4763):558–560. doi: 10.1126/science.2425436. [DOI] [PubMed] [Google Scholar]
  8. Gray M. A., Greenwell J. R., Argent B. E. Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells. J Membr Biol. 1988 Oct;105(2):131–142. doi: 10.1007/BF02009166. [DOI] [PubMed] [Google Scholar]
  9. Gray M. A., Harris A., Coleman L., Greenwell J. R., Argent B. E. Two types of chloride channel on duct cells cultured from human fetal pancreas. Am J Physiol. 1989 Aug;257(2 Pt 1):C240–C251. doi: 10.1152/ajpcell.1989.257.2.C240. [DOI] [PubMed] [Google Scholar]
  10. Gray M. A., Pollard C. E., Harris A., Coleman L., Greenwell J. R., Argent B. E. Anion selectivity and block of the small-conductance chloride channel on pancreatic duct cells. Am J Physiol. 1990 Nov;259(5 Pt 1):C752–C761. doi: 10.1152/ajpcell.1990.259.5.C752. [DOI] [PubMed] [Google Scholar]
  11. Gruenert D. C., Basbaum C. B., Welsh M. J., Li M., Finkbeiner W. E., Nadel J. A. Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5951–5955. doi: 10.1073/pnas.85.16.5951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Halm D. R., Rechkemmer G. R., Schoumacher R. A., Frizzell R. A. Apical membrane chloride channels in a colonic cell line activated by secretory agonists. Am J Physiol. 1988 Apr;254(4 Pt 1):C505–C511. doi: 10.1152/ajpcell.1988.254.4.C505. [DOI] [PubMed] [Google Scholar]
  13. Halm D. R., Rechkemmer G. R., Schoumacher R. A., Frizzell R. A. Apical membrane chloride channels in a colonic cell line activated by secretory agonists. Am J Physiol. 1988 Apr;254(4 Pt 1):C505–C511. doi: 10.1152/ajpcell.1988.254.4.C505. [DOI] [PubMed] [Google Scholar]
  14. Hanrahan J. W., Tabcharani J. A. Inhibition of an outwardly rectifying anion channel by HEPES and related buffers. J Membr Biol. 1990 Jun;116(1):65–77. doi: 10.1007/BF01871673. [DOI] [PubMed] [Google Scholar]
  15. Hwang T. C., Lu L., Zeitlin P. L., Gruenert D. C., Huganir R., Guggino W. B. Cl- channels in CF: lack of activation by protein kinase C and cAMP-dependent protein kinase. Science. 1989 Jun 16;244(4910):1351–1353. doi: 10.1126/science.2472005. [DOI] [PubMed] [Google Scholar]
  16. Jetten A. M., Yankaskas J. R., Stutts M. J., Willumsen N. J., Boucher R. C. Persistence of abnormal chloride conductance regulation in transformed cystic fibrosis epithelia. Science. 1989 Jun 23;244(4911):1472–1475. doi: 10.1126/science.2472008. [DOI] [PubMed] [Google Scholar]
  17. Krouse M. E., Hagiwara G., Chen J., Lewiston N. J., Wine J. J. Ion channels in normal human and cystic fibrosis sweat gland cells. Am J Physiol. 1989 Jul;257(1 Pt 1):C129–C140. doi: 10.1152/ajpcell.1989.257.1.C129. [DOI] [PubMed] [Google Scholar]
  18. Li M., McCann J. D., Anderson M. P., Clancy J. P., Liedtke C. M., Nairn A. C., Greengard P., Welsch M. J. Regulation of chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia. Science. 1989 Jun 16;244(4910):1353–1356. doi: 10.1126/science.2472006. [DOI] [PubMed] [Google Scholar]
  19. Li M., McCann J. D., Liedtke C. M., Nairn A. C., Greengard P., Welsh M. J. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature. 1988 Jan 28;331(6154):358–360. doi: 10.1038/331358a0. [DOI] [PubMed] [Google Scholar]
  20. McCann J. D., Li M., Welsh M. J. Identification and regulation of whole-cell chloride currents in airway epithelium. J Gen Physiol. 1989 Dec;94(6):1015–1036. doi: 10.1085/jgp.94.6.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Noonan K. E., Beck C., Holzmayer T. A., Chin J. E., Wunder J. S., Andrulis I. L., Gazdar A. F., Willman C. L., Griffith B., Von Hoff D. D. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7160–7164. doi: 10.1073/pnas.87.18.7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ponte P., Ng S. Y., Engel J., Gunning P., Kedes L. Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Res. 1984 Feb 10;12(3):1687–1696. doi: 10.1093/nar/12.3.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Quinton P. M. Cystic fibrosis: a disease in electrolyte transport. FASEB J. 1990 Jul;4(10):2709–2717. doi: 10.1096/fasebj.4.10.2197151. [DOI] [PubMed] [Google Scholar]
  24. Rich D. P., Anderson M. P., Gregory R. J., Cheng S. H., Paul S., Jefferson D. M., McCann J. D., Klinger K. W., Smith A. E., Welsh M. J. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature. 1990 Sep 27;347(6291):358–363. doi: 10.1038/347358a0. [DOI] [PubMed] [Google Scholar]
  25. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  26. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  27. Schoumacher R. A., Shoemaker R. L., Halm D. R., Tallant E. A., Wallace R. W., Frizzell R. A. Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells. Nature. 1987 Dec 24;330(6150):752–754. doi: 10.1038/330752a0. [DOI] [PubMed] [Google Scholar]
  28. Tabcharani J. A., Jensen T. J., Riordan J. R., Hanrahan J. W. Bicarbonate permeability of the outwardly rectifying anion channel. J Membr Biol. 1989 Dec;112(2):109–122. doi: 10.1007/BF01871272. [DOI] [PubMed] [Google Scholar]
  29. Tabcharani J. A., Low W., Elie D., Hanrahan J. W. Low-conductance chloride channel activated by cAMP in the epithelial cell line T84. FEBS Lett. 1990 Sep 17;270(1-2):157–164. doi: 10.1016/0014-5793(90)81257-o. [DOI] [PubMed] [Google Scholar]
  30. Welsh M. J. Abnormal regulation of ion channels in cystic fibrosis epithelia. FASEB J. 1990 Jul;4(10):2718–2725. doi: 10.1096/fasebj.4.10.1695593. [DOI] [PubMed] [Google Scholar]
  31. Welsh M. J., Li M., McCann J. D. Activation of normal and cystic fibrosis Cl- channels by voltage, temperature, and trypsin. J Clin Invest. 1989 Dec;84(6):2002–2007. doi: 10.1172/JCI114391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Welsh M. J., Liedtke C. M. Chloride and potassium channels in cystic fibrosis airway epithelia. 1986 Jul 31-Aug 6Nature. 322(6078):467–470. doi: 10.1038/322467a0. [DOI] [PubMed] [Google Scholar]
  33. Welsh M. J. Single apical membrane anion channels in primary cultures of canine tracheal epithelium. Pflugers Arch. 1986;407 (Suppl 2):S116–S122. doi: 10.1007/BF00584940. [DOI] [PubMed] [Google Scholar]
  34. Wine J. J. Basic aspects of cystic fibrosis. Clin Rev Allergy. 1991 Spring-Summer;9(1-2):1–28. doi: 10.1007/978-1-4612-0475-6_2. [DOI] [PubMed] [Google Scholar]
  35. Worrell R. T., Butt A. G., Cliff W. H., Frizzell R. A. A volume-sensitive chloride conductance in human colonic cell line T84. Am J Physiol. 1989 Jun;256(6 Pt 1):C1111–C1119. doi: 10.1152/ajpcell.1989.256.6.C1111. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES