Reduction in functional potency of the neurotoxin domoic acid in the presence of cadmium and zinc ions

The tricarboxylic neurotoxin domoic acid (DA) binds trace metals such as iron and copper. In vitro brain slice recording (area CA1 of rat hippocampal slices) was used to assess changes in DA potency in the presence of cadmium and zinc. Cadmium or zinc alone had little or no effect on CA1 responses. DA alone produced hyperexcitability and, with prolonged administration, a robust suppression of CA1 responses. Coadministration of DA with either 2 or 4 μM Cd2+ produced significant reductions in the potency of DA; less striking effects were seen in the presence of 4 μM Zn2+. These findings suggest that interactions of Cd2+ and Zn2+ with DA result in the formation of trace metal-neurotoxin complexes which are either unavailable for binding to ionotropic glutamate receptors, or bind without producing full agonist activity.