Abstract

The epileptic focus induced by pial surface iontophoresis of 100 μg divalent cobalt is confined to 130 mm 3 of supragranular ioscortex and contains aggregates of pyramidal neurons which are selectively impregnated by the heavy metal. At the time of initiation of epileptiform discharge, neuropathologic change is evident only at the ultrastructural level of resolution, manifested by severe swelling of pyramidal cell dendrites in the zone of cobalt deposition. When calcium and cobalt are simultaneously iontophoresed, epileptiform discharge and Golgi-like staining of pyramidal neurons does not occur, despite flooding of the cortical site with free or loosely bound cobalt complexes that can be completely removed by glutaraldehyde perfusion. In contrast, when perfusion-fixation is carried out at the initiation of cobalt-induced epileptiform discharge, the heavy metal can readily be identified within pyramidal cell dendrites as insoluble complexes which are tightly bound to cytoplasmic organelles. Based on these observations we suggest that cobalt-induced epileptiform discharge may result from a disturbance in calcium homeostasis which is triggered by high-affinity binding of the heavy metal within the cytoplasmic compartment of pyramidal cell dendrites.

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