title: CO2 permeability of cell membranes is regulated by membrane cholesterol and protein gas channels.
abstract: Recent observations that some membrane proteins act as gas channels seem surprising in view of the classical concept that membranes generally are highly permeable to gases. Here, we study the gas permeability of membranes for the case of CO(2), using a previously established mass spectrometric technique. We first show that biological membranes lacking protein gas channels but containing normal amounts of cholesterol (30-50 mol% of total lipid), e.g., MDCK and tsA201 cells, in fact possess an unexpectedly low CO(2) permeability (P(CO2)) of ∼0.01 cm/s, which is 2 orders of magnitude lower than the P(CO2) of pure planar phospholipid bilayers (∼1 cm/s). Phospholipid vesicles enriched with similar amounts of cholesterol also exhibit P(CO2) ≈ 0.01 cm/s, identifying cholesterol as the major determinant of membrane P(CO2). This is confirmed by the demonstration that MDCK cells depleted of or enriched with membrane cholesterol show dramatic increases or decreases in P(CO2), respectively. We demonstrate, furthermore, that reconstitution of human AQP-1 into cholesterol-containing vesicles, as well as expression of human AQP-1 in MDCK cells, leads to drastic increases in P(CO2), indicating that gas channels are of high functional significance for gas transfer across membranes of low intrinsic gas permeability.
authors.affiliation: Department of Chemistry, Universität Basel, Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Itel
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Samir
authors.forename: Fredrik
authors.initials: F
authors.lastname: Öberg
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chami
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Peter M T
authors.initials: PM
authors.lastname: Deen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meier
authors.forename: Kristina
authors.initials: K
authors.lastname: Hedfalk
authors.forename: Gerolf
authors.initials: G
authors.lastname: Gros
authors.forename: Volker
authors.initials: V
authors.lastname: Endeward
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002245:Carbon Dioxide / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism
chemical_list: C496020:AQP1 protein, human; D008051:Lipid Bilayers; D008081:Liposomes; D008565:Membrane Proteins; D010743:Phospholipids; D011510:Proteolipids; C020485:proteoliposomes; D002245:Carbon Dioxide; D051398:Aquaporin 1; D002784:Cholesterol