Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.
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.
Prudêncio
Miguel
M
Instituto de Medicina Molecular, Universidade de Lisboa, Portugal.
Derbyshire
Elvira T
ET
Marques
Catarina A
CA
Krishna
Sanjeev
S
Mota
Maria M
MM
Staines
Henry M
HM
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
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