title: Heavy metal cations permeate the TRPV6 epithelial cation channel.
abstract: TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland. gergely.kovacs@mci.unibe.ch
authors.forename: Gergely
authors.initials: G
authors.lastname: Kovacs
authors.forename: Tamas
authors.initials: T
authors.lastname: Danko
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Bergeron
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balazs
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Akos
authors.initials: A
authors.lastname: Zsembery
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002412:Cations; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D019216:Metals, Heavy / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D050916:TRPV Cation Channels / Q000378:metabolism*; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D019216:Metals, Heavy; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D002104:Cadmium; D015032:Zinc; D002118:Calcium; D016257:Fura-2