Characterisation of zinc uptake into rat cultured cerebrocortical oligodendrocyte progenitor cells.

In the mammalian brain, extracellular Zn(2+) is reported to play a neuromodulatory role and, during acute CNS injury, increased Zn(2+) release may be neurotoxic. Although several recent studies have examined possible mechanisms of neuronal Zn(2+) accumulation, little is known about oligodendroglial Zn(2+) uptake, the focus of the present study. 65Zn(2+) uptake was time-dependent and saturable (K(m)=3.2+/-1.0 microM, V(max)=697.2+/-67.3 pmoles mg protein(-1) 15 min(-1)). Neither kainate (an AMPA/kainate receptor agonist) nor nicardipine (an L-type Ca(2+) channel inhibitor) influenced 65Zn(2+) uptake, in contrast with pyrithione (a Zn(2+) ionophore). Either increasing extracellular H(+) concentration (pH 5.5) or co-application of either 100 microM Co(2+) or 100 microM Cu(2+) reduced (65)Zn(2+) uptake. However, 100 microM Fe(2+) failed to influence 65Zn(2+) uptake and 100 microM La(3+) increased 65Zn(2+) accumulation. These data are consistent with oligodendrocyte progenitor cells possessing a high-affinity Zn(2+) uptake mechanism similar to that described for the Zrt, Irt-like protein (ZIP) transporter family.