Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics, electrogenicity and trafficking.

Abstract The mouse Slc39a8 gene encodes the ZIP8 transporter, which has been shown to be a divalent cation/ HCO 3 - symporter. Using ZIP8 cRNA-injected Xenopus oocyte cultures, we show herein that: [a] ZIP8-mediated cadmium (Cd 2+ ) and zinc (Zn 2+ ) uptake have V max values of 1.8 ± 0.08 and 1.0 ± 0.08 pmol/oocyte/h, and K m values of 0.48 ± 0.08 and 0.26 ± 0.09 μM, respectively; [b] ZIP8-mediated Cd 2+ uptake is most inhibited by Zn 2+ , second-best inhibited by Cu 2+ , Pb 2+ and Hg 2+ , and not inhibited by Mn 2+ or Fe 2+ ; and [c] electrogenicity studies demonstrate an influx of two HCO 3 - anions per one Cd 2+ (or one Zn 2+ ) cation, i.e. electroneutral complexes. Using Madin–Darby canine kidney (MDCK) polarized epithelial cells retrovirally infected with ZIP8 cDNA and tagged with hemagglutinin at the C-terminus, we show that—similar to ZIP4—the ZIP8 eight-transmembrane protein is largely internalized during Zn 2+ homeostasis, but moves predominantly to the cell surface membrane (trafficking) under conditions of Zn 2+ depletion.