Effects of external calcium on zinc modulation of AMPA receptors

The effects of calcium on zinc modulation of current responses from two similar homomeric glutamate receptors, GluR1 and GluR3, was examined using the Xenopus oocyte expression system. Previous experiments carried out using normal (calcium-containing) physiological solution showed that kainate-evoked current responses from GluR3, but not from GluR1, were potentiated by low microM concentrations of zinc. Furthermore, this potentiation was observed only over a narrow range of zinc concentrations. In contrast, the present experiments demonstrated that in calcium-free solution (magnesium replacement) zinc can potentiate both GluR3, as expected, but also GluR1. In addition, the potentiation occurs over a large range of zinc concentrations (> 2 log units). Re-supply of calcium to the solution interferes with zinc potentiation in a concentration-dependent manner. When supernormal concentrations of calcium are present, zinc greatly inhibits currents at zinc concentrations that would cause potentiation in the absence of calcium, and that would cause smaller inhibition in normal solution. Because zinc is co-released along with neurotransmitter at many glutamatergic synapses in vertebrate brains, and synaptic calcium levels are subject to variable control, calcium regulation of zinc sensitivity may be physiologically relevant.