EFFECTS OF EXTERNAL CALCIUM ON ZINC MODULATION OF AMPA RECEPTORS

The effects of calcium on zinc modulation of current responses from tw o similar homomeric glutamate receptors, GluR1 and GluR3, was examined using the Xenopus oocyte expression system. previous experiments carr ied out using normal (calcium-containing physiological solution showed that kainate-evoked current responses from GluR3, but not from GluR1, were potentiated by low mu M concentrations of zinc. Furthermore, thi s potentiation was observed only over a narrow range of zinc concentra tions. In contrast, the present experiments demonstrated that in calci um-free solution (magnesium replacement) zinc can potentiate both GluR 3, as expected, but also GluR1. In addition, the potentiation occurs o ver a large range of zinc concentrations (> 2 log units). Re-supply of calcium to the solution interferes with zinc potentiation in a concen tration-dependent manner. When supernormal concentrations of calcium a re present, zinc greatly inhibits currents at zinc concentrations that would cause potentiation in the absence of calcium, and that would ca use smaller inhibition in normal solution. Because zinc is co-released along with neurotransmitter at many glutamatergic synapses in vertebr ate brains, and synaptic calcium levels are subject to variable contro l, calcium regulation of zinc sensitivity may be physiologically relev ant, (C) 1997 Elsevier Science B.V.