Zinc influx and physiological consequences in the β-insulinoma cell line, Min6

• Published in: Biochemical and biophysical research communications 2006-07, Vol.346 (1), p.205-212
• Main Authors: Priel, Tsvia, Hershfinkel, Michal
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - physiology; Cell Line, Tumor; Cell Survival - drug effects; Insulinoma - metabolism; L-type calcium channels; Mice; Nimodipine - pharmacology; Pancreatic Neoplasms - metabolism; Pancreatic β-cells; Zinc; Zinc - metabolism; Zinc - pharmacology; Zinc toxicity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.05.104

In the mammalian pancreas, high concentrations of Zn 2+ are co-secreted with insulin, which may then permeate via abundant L-type Ca 2+ channels (LTCC) present on the β-cells. Neither the mechanisms utilized by these cells to lower cytosolic Zn 2+ nor the implications of increased intracellular Zn 2+ on β-cell survival are well understood. To address this, we employed cell imaging of Zn 2+ and Ca 2+ in the β-insulinoma cell line, Min6. Depolarization induced an intense zinc influx that was blocked by nifedipine and verapamil, indicating that Zn 2+ permeates via the LTCC. Both Ca 2+ and Zn 2+ permeated concomitantly, yet while Ca 2+ was subsequently removed from the cytosol, Zn 2+ was retained in the cells. Fluorescent staining of vesicular Zn 2+ using ZP1 demonstrated that Zn 2+ could be slowly sequestered following a brief exposure to low concentration of Zn 2+. In contrast, cells were unable to sequester Zn 2+ following application of high concentrations, which was followed by massive cell death. Our results demonstrate homeostatic crosstalk between the plasma membrane and intracellular zinc transporters and suggest that attenuating zinc influx may enhance β-cell survival.