Premium
Heavy metal cations permeate the TRPV6 epithelial cation channel
Author(s) -
Kovacs Gergely,
Danko Tamas,
Bergeron Marc J,
Balazs Bernadett,
Suzuki Yoshiro,
Zsembery Akos,
Hediger Matthias
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1042.23
Subject(s) - metal , permeation , chemistry , environmental chemistry , trpv6 , channel (broadcasting) , environmental science , membrane , calcium , biochemistry , organic chemistry , engineering , voltage dependent calcium channel , electrical engineering
TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This highly Ca 2+ ‐selective channel is expressed in the duodenum and the placenta, where it is responsible for Ca 2+ absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to Ca 2+ but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as Zn 2+ and Cd 2+ . We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non‐transfected cells, and that the difference almost disappeared in nominally Ca 2+ ‐free solution. Live cell imaging experiments with Fura‐2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability to Ca 2+ , Ba 2+ , Sr 2+ , Mn 2+ , Zn 2+ , Cd 2+ , and interestingly also to La 3+ and Gd 3+ . These results were confirmed using the patch clamp technique. Furthermore, 45 Ca 2+ uptake experiments showed that Cd 2+ , La 3+ and Gd 3+ are efficient inhibitors of TRPV6‐mediated Ca 2+ influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in Ca 2+ transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.