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. 1996 Oct 1;496(Pt 1):69–80. doi: 10.1113/jphysiol.1996.sp021666

Properties of the cAMP-activated C1- current in choroid plexus epithelial cells isolated from the rat.

J D Kibble 1, A E Trezise 1, P D Brown 1
PMCID: PMC1160825  PMID: 8910197

Abstract

1. This study used whole-cell patch clamp and RNA in situ hybridization experiments to determine whether the cAMP-activated C1- current expressed in choroid plexus epithelial cells was carried by the cystic fibrosis transmembrane conductance regulator (CFTR) channel. 2. In patch clamp experiments, inclusion of 0.25 mM cAMP and 375 protein kinase A catalytic subunit (PKA) in the electrode solution caused activation of an inwardly rectifying current (21/23 cells). This current was C1- selective, since the current reversal potential (Erev) was -31 +/- 3 mV with equilibrium potential values for C1- (EC1) and Na+ (ENa) of -44 and 0 mV, respectively. 3. In anion substitution experiments, the relative anion permeability sequence for the inward rectifier was: I- (3.5) > HCO3-(1.5) = C1-(1.0) > Br-(0.6) > aspartate (0.2). 4. The inward rectifier was sensitive to inhibition by a range of known channel inhibitors, including: glibenclamide (100 microns), DIDS (100 and 500 microns), NPPB (100 microns) and Ba2+ (1 mM). 5. In RNA in situ hybridization experiments, using two independent rat CFTR cRNA probes, expression of CFTR could not be detected in epithelial cells from the rat choroid plexus. 6. In conclusion, the cAMP-dependent whole-cell C1- current present in choroid plexus epithelial cells from the rat has properties which are distinctly different from those of CFTR.

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Selected References

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  1. Anderson M. P., Gregory R. J., Thompson S., Souza D. W., Paul S., Mulligan R. C., Smith A. E., Welsh M. J. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science. 1991 Jul 12;253(5016):202–205. doi: 10.1126/science.1712984. [DOI] [PubMed] [Google Scholar]
  2. Demarest J. R., Loo D. D., Sachs G. Activation of apical chloride channels in the gastric oxyntic cell. Science. 1989 Jul 28;245(4916):402–404. doi: 10.1126/science.2474200. [DOI] [PubMed] [Google Scholar]
  3. Deng Q. S., Johanson C. E. Cyclic AMP alteration of chloride transport into the choroid plexus-cerebrospinal fluid system. Neurosci Lett. 1992 Aug 31;143(1-2):146–150. doi: 10.1016/0304-3940(92)90253-4. [DOI] [PubMed] [Google Scholar]
  4. Engelhardt J. F., Yankaskas J. R., Ernst S. A., Yang Y., Marino C. R., Boucher R. C., Cohn J. A., Wilson J. M. Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet. 1992 Nov;2(3):240–248. doi: 10.1038/ng1192-240. [DOI] [PubMed] [Google Scholar]
  5. Epstein M. H., Feldman A. M., Brusilow S. W. Cerebrospinal fluid production: stimulation by cholera toxin. Science. 1977 May 27;196(4293):1012–1013. doi: 10.1126/science.193189. [DOI] [PubMed] [Google Scholar]
  6. Fuller C. M., Benos D. J. CFTR! Am J Physiol. 1992 Aug;263(2 Pt 1):C267–C286. doi: 10.1152/ajpcell.1992.263.2.C267. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Hincke M. T., Nairn A. C., Staines W. A. Cystic fibrosis transmembrane conductance regulator is found within brain ventricular epithelium and choroid plexus. J Neurochem. 1995 Apr;64(4):1662–1668. doi: 10.1046/j.1471-4159.1995.64041662.x. [DOI] [PubMed] [Google Scholar]
  9. Kartner N., Hanrahan J. W., Jensen T. J., Naismith A. L., Sun S. Z., Ackerley C. A., Reyes E. F., Tsui L. C., Rommens J. M., Bear C. E. Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance. Cell. 1991 Feb 22;64(4):681–691. doi: 10.1016/0092-8674(91)90498-n. [DOI] [PubMed] [Google Scholar]
  10. Kotera T., Brown P. D. Cl- current activation in choroid plexus epithelial cells involves a G protein and protein kinase A. Am J Physiol. 1994 Feb;266(2 Pt 1):C536–C540. doi: 10.1152/ajpcell.1994.266.2.C536. [DOI] [PubMed] [Google Scholar]
  11. Kotera T., Brown P. D. Evidence for two types of potassium current in rat choroid plexus epithelial cells. Pflugers Arch. 1994 Jun;427(3-4):317–324. doi: 10.1007/BF00374540. [DOI] [PubMed] [Google Scholar]
  12. Kubo M., Okada Y. Volume-regulatory Cl- channel currents in cultured human epithelial cells. J Physiol. 1992 Oct;456:351–371. doi: 10.1113/jphysiol.1992.sp019340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Malinowska D. H., Kupert E. Y., Bahinski A., Sherry A. M., Cuppoletti J. Cloning, functional expression, and characterization of a PKA-activated gastric Cl- channel. Am J Physiol. 1995 Jan;268(1 Pt 1):C191–C200. doi: 10.1152/ajpcell.1995.268.1.C191. [DOI] [PubMed] [Google Scholar]
  14. Moorman J. R., Ackerman S. J., Kowdley G. C., Griffin M. P., Mounsey J. P., Chen Z., Cala S. E., O'Brian J. J., Szabo G., Jones L. R. Unitary anion currents through phospholemman channel molecules. Nature. 1995 Oct 26;377(6551):737–740. doi: 10.1038/377737a0. [DOI] [PubMed] [Google Scholar]
  15. Moorman J. R., Palmer C. J., John J. E., 3rd, Durieux M. E., Jones L. R. Phospholemman expression induces a hyperpolarization-activated chloride current in Xenopus oocytes. J Biol Chem. 1992 Jul 25;267(21):14551–14554. [PubMed] [Google Scholar]
  16. Overholt J. L., Saulino A., Drumm M. L., Harvey R. D. Rectification of whole cell cystic fibrosis transmembrane conductance regulator chloride current. Am J Physiol. 1995 Mar;268(3 Pt 1):C636–C646. doi: 10.1152/ajpcell.1995.268.3.C636. [DOI] [PubMed] [Google Scholar]
  17. Pusch M., Neher E. Rates of diffusional exchange between small cells and a measuring patch pipette. Pflugers Arch. 1988 Feb;411(2):204–211. doi: 10.1007/BF00582316. [DOI] [PubMed] [Google Scholar]
  18. Saito Y., Wright E. M. Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides. J Physiol. 1983 Mar;336:635–648. doi: 10.1113/jphysiol.1983.sp014602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saito Y., Wright E. M. Regulation of bicarbonate transport across the brush border membrane of the bull-frog choroid plexus. J Physiol. 1984 May;350:327–342. doi: 10.1113/jphysiol.1984.sp015204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schwiebert E. M., Egan M. E., Hwang T. H., Fulmer S. B., Allen S. S., Cutting G. R., Guggino W. B. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell. 1995 Jun 30;81(7):1063–1073. doi: 10.1016/s0092-8674(05)80011-x. [DOI] [PubMed] [Google Scholar]
  21. Segal M. B. Extracellular and cerebrospinal fluids. J Inherit Metab Dis. 1993;16(4):617–638. doi: 10.1007/BF00711896. [DOI] [PubMed] [Google Scholar]
  22. Sheppard D. N., Welsh M. J. Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J Gen Physiol. 1992 Oct;100(4):573–591. doi: 10.1085/jgp.100.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stutts M. J., Canessa C. M., Olsen J. C., Hamrick M., Cohn J. A., Rossier B. C., Boucher R. C. CFTR as a cAMP-dependent regulator of sodium channels. Science. 1995 Aug 11;269(5225):847–850. doi: 10.1126/science.7543698. [DOI] [PubMed] [Google Scholar]
  24. Thiemann A., Gründer S., Pusch M., Jentsch T. J. A chloride channel widely expressed in epithelial and non-epithelial cells. Nature. 1992 Mar 5;356(6364):57–60. doi: 10.1038/356057a0. [DOI] [PubMed] [Google Scholar]
  25. Trapnell B. C., Chu C. S., Paakko P. K., Banks T. C., Yoshimura K., Ferrans V. J., Chernick M. S., Crystal R. G. Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6565–6569. doi: 10.1073/pnas.88.15.6565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Trezise A. E., Buchwald M. In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator. Nature. 1991 Oct 3;353(6343):434–437. doi: 10.1038/353434a0. [DOI] [PubMed] [Google Scholar]
  27. Trezise A. E., Linder C. C., Grieger D., Thompson E. W., Meunier H., Griswold M. D., Buchwald M. CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents. Nat Genet. 1993 Feb;3(2):157–164. doi: 10.1038/ng0293-157. [DOI] [PubMed] [Google Scholar]

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