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

The mouse Slc39a8   gene encodes the ZIP8 transporter, which has been shown to be a divalent cation/HCO3- symporter. Using ZIP8 cRNA-injected Xenopus oocyte cultures, we show herein that: [a] ZIP8-mediated cadmium (Cd2+) and zinc (Zn2+) uptake have Vmax values of 1.8 ± 0.08 and 1.0 ± 0.08 pmol/oocyte/h, and Km values of 0.48 ± 0.08 and 0.26 ± 0.09 μM, respectively; [b] ZIP8-mediated Cd2+ uptake is most inhibited by Zn2+, second-best inhibited by Cu2+, Pb2+ and Hg2+, and not inhibited by Mn2+ or Fe2+; and [c] electrogenicity studies demonstrate an influx of two HCO3- anions per one Cd2+ (or one Zn2+) 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 Zn2+ homeostasis, but moves predominantly to the cell surface membrane (trafficking) under conditions of Zn2+ depletion.