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Ein Flip-Flop-Modell des Chlorid-Kanal-Komplexes erklärt die Fehlregulation des Chloridflusses am Plasmalemm von Zellen bei der cystischen Fibrose

A flip flop model of the chloride channel complex explains the misregulation of chloride in the plasmalemm of cells in cystic fibrosis

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Summary

The basic defect in cystic fibrosis is the chloride impermeability of the plasmalemm in different cells. A candidate for the chloride channel, thought to be affected in the syndrome, is “Porin 31HL” recently described by us. The molecule is i) expressed in the plasmalemm of different cells, it has ii) a molecular mass of 31000 Daltons, it shows iii) high conductance in artificial membranes and it can be iv) modified by 4,4′-Diisothiocyana-tostilben-2,2′-disulfonat. A porin in the outer membrane of cells should furthermore v) be regulated by modulators. All these characters of “Porin 31HL” correspond to those given in literature for chloride channels. The regulation of the channels can be explained by a two component flip flop model.

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Abbreviations

CF:

Cystische Fibrose

CFTR:

Cystic Fibrosis Transmembrane Conductance Regulator

DIDS:

4,4′-Diisothiocyanatostilben-2,2′-disulfonat

kDa:

kilo Daltons

NPPB:

5-Nitro-2-(3-Phenylpropylamino)benzoat

SDS-PAGE:

Natriumdodecylsulfat Polyacrylamid Gelelektrophorese

2D-PAGE:

Zweidimensionale Polyacrylamid Gelelektrophorese

VDAC:

voltage dependent anion channel

Literatur

  • Adams V, Bosch W, Schlegel J, Wallimann T, Brdiczka D (1989) Further characterization of contact sites from mitochondria of different tissues: topology of peripheral kinases. Biochim Biophys Acta 981:213–225

    Google Scholar 

  • Bear CE (1988) Phosphorylation-activated chloride channels in human skin fibroblasts. FEBS Letters 237:145–149

    Google Scholar 

  • Benz R (1990) Biophysical properties of porin pores from mitochondrial outer membrane of eukaryotic cells. Experientia 46:131–137

    Google Scholar 

  • Benz R, Wojtczak L, Bosch W, Brdiczka D (1988) Inhibition of adenine nucleotide transport through the mitochondrial porin by a synthetic polyanion. FEBS Letters 231:75–80

    Google Scholar 

  • Benz R, Kottke M, Brdiczka D (1990) The cationically selective state of the mitochondrial outer membrane pore: a study with intact mitochondria and reconstituted mitochondrial porin. Biochim Biophys Acta 1022:311–318

    Google Scholar 

  • Blatz AL, Magleby KL (1983) Single voltage-dependent chloride-selective channels of large conductance in cultured rat muscle. Biophys J 43:237–241

    Google Scholar 

  • Breuer W (1990) Reconstitution of a kidney chloride channel and its identification by covalent labeling. Biochim Biophys Acta 1022:229–236

    Google Scholar 

  • Chen JH, Schulman H, Gardner P (1989) A cAMP-regulated chloride channel in lymphocytes that is affected in cystic fibrosis. Science 243:657–660

    Google Scholar 

  • Cohn JA (1990) Protein kinase C mediates cholinergically regulated protein phosphorylation in a Cl−-secreting epithelium. Am J Physiol 258:C227-C233

    Google Scholar 

  • Colombini M, Holden MJ, Mangan PS (1989) Modulation of the mitochondrial channel VDAC by a variety of agents. In: Azzi A et al. (eds) Anion carriers of mitochondrial membranes. Springer, Berlin Heidelberg, pp 215–224

    Google Scholar 

  • De Pinto V, Ludwig O, Krause J, Benz R, Palmieri F (1987) Porin pores of mitochondrial outer membranes from high and low eukaryotic cells: biochemical and biophysical characterization. Biochim Biophys Acta 894:109–119

    Google Scholar 

  • Drumm ML, Pope HA, Cliff WH, Rommens JM, Marvin SA, Tsui L-C, Collins FS, Frizzell RA, Wilson JM (1990) Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell 62:1227–1233

    Google Scholar 

  • Gögelein H (1988) Chloride channels in epithelia. Biochim Biophys Acta 947:521–547

    Google Scholar 

  • Gregory RJ, Chen SH, Rich DP, Marshall J, Paul S, Hehir K, Ostedgaard L, Klinger KW, Welsh MJ, Smith AE (1990) Expression and characterization of the cystic fibrosis transmembrane conductance regulator. Nature 347:382–386

    Google Scholar 

  • Holden MJ, Colombini M (1988) The mitochondrial outer membrane channel, VDAC, is modulated by a soluble protein. FEBS Letters 241:105–109

    Google Scholar 

  • Hoshi T, Zagotta WN, Aldrich RW (1990) Biophysical and molecular mechanisms of shaker potassium channel inactivation. Science 250:533–538

    Google Scholar 

  • Hyde SC, Emsley P, Hartshorn MJ, Mimmack MM, Gileadi U, Pearce SR, Gallagher MP, Gill DR, Hubbard RE, Higgins CF (1990) Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature 346:362–365

    Google Scholar 

  • Kanno T, Takishima T (1990) Chloride and potassium channels in U937 human monocytes. J Membrane Biol 116:149–161

    Google Scholar 

  • Kayser H, Kratzin HD, Thinnes FP, Götz H, Schmidt WE, Eckart K, Hilschmann N (1989) Zur Kenntnis der Porine des Menschen II. Charakterisierung und Primärstruktur eines 31-kDa-Porins aus menschlichen B-Lymphozyten (Porin 31HL). Biol Chem Hoppe-Seyler 370:1265–1278

    Google Scholar 

  • Kunzelmann K, Pavenstädt H, Greger R (1989) Properties and regulation of chloride channels in cystic fibrosis and normal airway cells. Pflügers Arch 415:172–182

    Google Scholar 

  • Landry DW, Akabas MH, Redhead C, Edelman A, Cragoe EJ Jr, Al-Awqati Q (1989) Purification and reconstitution of chloride channels from kidney and trachea. Science 244:1469–1472

    Google Scholar 

  • Li M, McCann JD, Welsh MJ (1990) Apical membrane Cl− channels in airway epithelia: anion selectivity and effect of an inhibitor. Am J Physiol 259:C295-C301

    Google Scholar 

  • Manella CA, Guo X-W (1990) Interaction between the VDAC channel and a polyanionic effector. An electron microscopic study. Biophys J 57:23–31

    Google Scholar 

  • Parham P (1990) Transporters of delight. Nature 348:674–675

    Google Scholar 

  • Quinton PM (1990a) Cystic fibrosis: a disease in electrolyte transport. FASEB J 4:2709–2717

    Google Scholar 

  • Quinton PM (1990b) Righting the wrong protein. Nature 347:226

    Google Scholar 

  • Rich DP, Anderson MP, Gregory RJ, Cheng SH, Paul S, Jefferson DM, McCann JD, Klinger KW, Smith AE, Welsh MJ (1990) Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature 347:358–363

    Google Scholar 

  • Ringe D, Petsko GA (1990) Cystic fibrosis. A transport problem? Nature 346:312–313

    Google Scholar 

  • Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou J-L, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245:1066–1073

    Google Scholar 

  • Schlichter LC, Grygorczyk R, Pahapill PA, Grygorczyk C (1990) A large, multiple-conductance chloride channel in normal human T lymphocytes. Pflügers Arch 416:413–421

    Google Scholar 

  • Schwarze W, Kolb H-A (1984) Voltage-dependent kinetics of an anionic channel of large unit conductance in macrophages and myotube membranes. Pflügers Arch 402:281–291

    Google Scholar 

  • Stutts MJ, Gatzy JT, Boucher RC (1988) Effects of metabolic inhibition on ion transport by dog bronchial epithelium. J Appl Physiol 64:253–258

    Google Scholar 

  • Thinnes FP, Hilschmann N, Kayser H, Götz H (1983) Ist das HLA-DR-assoziierte Glycoprotein p31 ein ubiquitäres Molekül? Hoppe-Seyler's Z Physiol Chem 364:1805–1811

    Google Scholar 

  • Thinnes FP, Meyer A, von Schwartzenberg K (1984) On a basic 31 kDa muscle membrane protein in cattle and pig, presumably equivalent to the class II antigen associated p31 molecule. Anim Blood Groups and Biochem Gen 15:181–189

    Google Scholar 

  • Thinnes FP, Götz H, Kayser H, Benz R, Schmidt WE, Kratzin HD, Hilschmann N (1989) Zur Kenntnis der Porine des Menschen I. Reinigung eines Porins aus menschlichen B-Lymphozyten (Porin 31HL) und sein topochemischer Nachweis auf dem Plasmalemm der Herkunftszelle. Biol Chem Hoppe-Seyler 370:1253–1264

    Google Scholar 

  • Thinnes FP, Schmid A, Benz R, Hilschmann N (1990) Studies on human porin III. Does the voltage-dependent anion channel “Porin 31HL” form part of the chloride channel complex, which is observed in different cells and thought typ be affected in cystic fibrosis? Biol Chem Hoppe-Seyler 371:1047–1050

    Google Scholar 

  • Welsh MJ (1990) Abnormal regulation of ion channels in cystic fibrosis epithelia. FASEB J 4:2718–2725

    Google Scholar 

  • Welsh MJ, Li M, McCann JD (1989) Activation of normal and cystic fibrosis Cl− channels by voltage, temperature, and trypsin. J Clin Invest 84:2002–2007

    Google Scholar 

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Authors and Affiliations

  1. Abteilung Immunchemie, Max-Planck-Institut für Experimentelle Medizin, Göttingen

    F. P. Thinnes, D. Babel, A. Hein, L. Jürgens, U. König & N. Hilschmann

  2. Lehrstuhl für Biotechnologie der Universität Würzburg, Deutschland

    A. Schmid

Authors
  1. F. P. Thinnes
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  2. D. Babel
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  3. A. Hein
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  4. L. Jürgens
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  5. U. König
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  6. A. Schmid
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  7. N. Hilschmann
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Additional information

The model was presented for the first time in the 12th Magdeburg Colloquium on Mitochondrial Functions, 9–10 November 1990, in Magdeburg and will be discussed here more detailed.

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Thinnes, F.P., Babel, D., Hein, A. et al. Ein Flip-Flop-Modell des Chlorid-Kanal-Komplexes erklärt die Fehlregulation des Chloridflusses am Plasmalemm von Zellen bei der cystischen Fibrose. Klin Wochenschr 69, 283–288 (1991). https://doi.org/10.1007/BF01644755

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  • DOI: https://doi.org/10.1007/BF01644755

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