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Intrinsic CO 2 permeability of cell membranes and role of CO 2 channels

Intrinsic CO 2 permeability of cell membranes and role of CO 2 channels. Volker Endeward, Fabian Itel, Samer Al-Samir, Mohamed Chami, Fredrik Öberg, Kristina Hedfalk, Gerolf Gros. Intrinsic CO 2 permeability of a red cell membrane. Gas permeability of synthetic phospholipid bilayers.

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Intrinsic CO 2 permeability of cell membranes and role of CO 2 channels

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  1. Intrinsic CO2 permeability of cell membranes and role of CO2 channels Volker Endeward, Fabian Itel, Samer Al-Samir, Mohamed Chami, Fredrik Öberg,Kristina Hedfalk,Gerolf Gros

  2. Intrinsic CO2 permeability of a red cell membrane

  3. Gas permeability of synthetic phospholipid bilayers Alberts et al. Molecular Biology Of The Cell, 4th Edition

  4. CO2 ? 1. What are the intrinsic CO2 permeabilities of cell membranes? • Which mechanisms are responsible for the given intrinsic • permeabilities of cell membranes?

  5. 1. What are the intrinsic CO2 permeabilities of cell membranes?

  6. Mass spectrometer H 16 O + C 18 O 16 O 2/ 3 2 HC 18 O 16 O - + H + 2 1/ 3 H 18 O + C 16 O 2 2 P HCO3 - P H2O P CO2 H 18 O + C 16 O 1/3 2 2 H C 18 O 16 O - + H + CA 2 2/3 H 16 O + C 18 O 16 O 2 Cell

  7. Cell membranes show CO2 permeabilities lower then synthetic lipid bilayer

  8. Which mechanisms are responsible for the given intrinsic • permeabilities of cell membranes?

  9. PC:PS:Chol – vesicles with different cholesterol content PC = Phosphatidylcholine PS = Phosphatidylserine Chol = Cholesterol (0 – 70%) Ø = ~ 150 nm

  10. 70% chol. [C18O16O] - [C18O16O]∞ (µM) 30% chol.

  11. Effect of cholesterol on lipid vesicle CO2 permeability >0.16 cm/s PC:PS = 8:2

  12. Comparison of cell membranes and cholesterol-containing vesicles

  13. CO2 permeabilities of cell membranes appear to be essentially determined by their cholesterol content

  14. cholesterol depletion with β-cyclodextrin cholesterol enrichment with β-cyclodextrin

  15. Is cholesterol the cause of the low CO2 permeability ofMDCK cells? Reduction of cholesterol with cyclodextrin raises PCO2. Enrichment with cholesterol lowers PCO2 compared to normal cells.

  16. We show that cell membranes possess a low intrinsic CO2 permeability, often in the range of 0.01 cm/s. • This permeability is 2, and in one case 3, orders of magnitude lower than the CO2 permeability of pure artificial phospholipid bilayers. • The main cause of this low CO2 permeability is the cholesterol content of the cell membrane. With increasing cholesterol content PCO2 decreases • in artificial vesicles as well as in intact cells.

  17. Physiological consequences of low CO2 membrane permeabilities 1. Consequences of the extremely low CO2 permeability of the apical membrane of colon epithelium 2. Effect of low CO2 membrane permeability on red blood cell gas exchange

  18. PCO2 = 0.0015 cm/s Consequences of low apical CO2 permeability in colonocytes apical membrane basal membrane 100 colon lumen pCO 2 ( mmHg ) capillary 40 20 0 diffusion pathway (µm)

  19. Example of a cell with a high gas exchange: red blood cell

  20. From these considerations we can see that gas exchange of cells with • a low CO2 permeability is limited. • Hypothesis: cell membranes with normal cholesterol and low intrinsic PCO2 adapt their CO2 permeabilities to their needs by incorporating gas chanels in the membrane.

  21. AQP1 AqpZ

  22. Aquaporin 1 as a CO2 channel in cholesterol-containing lipid vesicles PC:PS:Chol 8:2:10 Incorporation of AQP1 into vesicles causes a rise in PCO2 Change of PCO2 in vesicles with decreasing Lipid- Protein-Ratios (LPR)

  23. DIDS reduces the CO2 permeability of AQP1 containing vesicles

  24. Aquaporin 1 as a CO2 channel in MDCK cells Expression of AQP1 in MDCK cells raises PCO2

  25. We conclude that in a membrane of normal cholesterol content and low CO2 permeability, incorporation of AQP1 into the membrane significantly increases the CO2 permeability in a concentration dependent manner. • AQP1 acts as a DIDS-sensitive CO2 channel.

  26. Summary With rising cholesterol content the CO2 permeability ( PCO2) of lipid vesicles decreases drastically. The intrinsic PCO2 of cell membranes is low due to their cholesterol content: 1) cell membranes and lipid vesicles with identical cholesterol content exhibit identical CO2 permeability 2) cholesterol-depleted cell membranes have an increased CO2 permeability, cholesterol-enriched cell membranes a reduced permeability Cell membranes with normal cholesterol raise their CO2 permeability, when functionally required, by incorporation of CO2 channels: 1) AQP1 incorporated in lipid vesicles raises CO2 permeability in a concentration-dependent manner 2) AQP1 expression in MDCK cells increases membrane PCO2.

  27. Medizinische Hochschule Hannover Vegetative Physiologie Samer Al-Samir Timo Meine Werner Zingel Gerolf Gros Universität BaselDept. Chemie / Biozentrum Fabian Itel Mohamed Chami University of GothenburgDept. Chemistry/Biochemistry Frederic Öberg Kristina Hedfalk

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