title: Whole cell Cl- conductances in mouse choroid plexus epithelial cells do not require CFTR expression.
abstract: Whole cell patch-clamp studies were performed with tissue isolated from the cystic fibrosis (CF) transgenic Cftrm1cam mouse, to determine whether anion currents in choroid plexus epithelial cells require the expression of cystic fibrosis transmembrane conductance regulator (CFTR). Inclusion of 0.25 mM adenosine 3',5'-cyclic monophosphate (cAMP) and 375 nM protein kinase A (PKA) in the pipette solution caused a significant activation of a Cl(-)-selective, inward-rectifying conductance in cells from wild-type and CF mice. The small, outward currents observed in wild-type and CF animals, however, were not activated by cAMP-PKA. There were no significant differences in the size of currents between wild-type, heterozygote, and CF cells in the presence or absence of cAMP-PKA. A second whole cell conductance was activated when cells from wild-type mice were swollen. These volume-activated currents were Cl- selective and exhibited outward rectification. They were Ca2+ independent and ATP dependent and blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid. The volume-activated channels were also activated in CF mutant cells, and there was no significant difference in the size of the volume-activated currents between wild-type, heterozygote, and CF cells. It is concluded that CFTR neither contributes to the whole cell conductance nor regulates the other anion conductances in choroid plexus epithelial cells.
authors.affiliation: Cell Physiology Group, School of Biological Sciences, University of Manchester, United Kingdom.
authors.forename: J D
authors.initials: JD
authors.lastname: Kibble
authors.forename: C
authors.initials: C
authors.lastname: Garner
authors.forename: W H
authors.initials: WH
authors.lastname: Colledge
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: H
authors.initials: H
authors.lastname: Kajita
authors.forename: M
authors.initials: M
authors.lastname: Evans
authors.forename: P D
authors.initials: PD
authors.lastname: Brown
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002831:Choroid Plexus / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016296:Mutagenesis; D009994:Osmolar Concentration
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases