title: Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.
abstract: Parasite infection can lead to alterations in the permeability of host plasma membranes. Presented here is the first demonstration that this phenomenon occurs in Plasmodium-infected liver cells. Using the whole-cell patch-clamp technique, volume-regulated anion channel (VRAC) activity was characterized in Huh-7 cells (a human hepatoma cell line) before and after infection with Plasmodium berghei. Consistent with the presence of VRACs, hypotonic bath solution induced large ion currents in Huh-7 cells that rectified outwardly, reversed close to the equilibrium potential for Cl(-) and were inhibited by tamoxifen, clomiphene, mefloquine and 5-nitro-2, 3-(phenylpropylamino)-benzoic acid (NPPB), with IC(50) values of 4 +/- 1, 4 +/- 2, 2 +/- 1 and 52 +/- 12 microM respectively. In isotonic conditions, initial current recordings measured in uninfected and immature (24 h post invasion) parasite-infected Huh-7 cells were similar (with conductances of 14 +/- 3 versus 19 +/- 5 pS/pF). However, in mature (48-72 h post invasion) parasite-infected Huh-7 cells there was a sevenfold increase in currents (with a conductance of 98 +/- 16 pS/pF). The elevated currents observed in the latter are consistent with VRAC-like activity and the possible reasons for their activation are discussed.
authors.affiliation: Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.forename: Elvira T
authors.initials: ET
authors.lastname: Derbyshire
authors.forename: Catarina A
authors.initials: CA
authors.lastname: Marques
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.forename: Henry M
authors.initials: HM
authors.lastname: Staines
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D048429:Cell Size; D002713:Chlorine / Q000378:metabolism; D002996:Clomiphene / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022781:Hepatocytes / Q000469:parasitology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D015767:Mefloquine / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D010962:Plasmodium berghei / Q000254:growth & development*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D000838:Anions; D004791:Enzyme Inhibitors; D007473:Ion Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; D002996:Clomiphene; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D002713:Chlorine; D015767:Mefloquine