Heavy metal cations permeate the TRPV6 epithelial cation channel
| Autor: | Matthias A. Hediger, Ákos Zsembery, Tamas Danko, Yoshiro Suzuki, Bernadett Balázs, Marc J. Bergeron, Gergely Kovacs |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cell Membrane Permeability
Patch-Clamp Techniques Time Factors TRPV6 Physiology Recombinant Fusion Proteins Inorganic chemistry Intracellular Space TRPV Cation Channels chemistry.chemical_element Breast Neoplasms Calcium Biochemistry Calcium in biology Divalent 03 medical and health sciences Imaging Three-Dimensional 0302 clinical medicine Cations Cell Line Tumor Metals Heavy Genetics Humans Patch clamp Molecular Biology Fluorescent Dyes 030304 developmental biology chemistry.chemical_classification Calcium metabolism 0303 health sciences Cadmium Calcium channel Reproducibility of Results Epithelial Cells Cell Biology Zinc HEK293 Cells chemistry Biophysics Female Fura-2 Ion Channel Gating 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Cell calcium |
| DOI: | 10.1016/j.ceca.2010.11.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|