CYANIDE INDUCES PROTEIN-KINASE-C TRANSLOCATION - BLOCKADE BY NMDA ANTAGONISTS

Activation and translocation of protein kinase C (PKC) during KCN-indu ced histotoxic hypoxia was studied in rat brain slices prepared from c erebellum, hippocampus, and cortex. Treatment with 1-10 mM KCN produce d a significant increase in PKC translocation and enzyme activity in t he particulate fraction of cerebellar and hippocampal slices. In corti cal slices, PKC activity was not affected by cyanide treatment. The me mbrane-associated PKC activity reached a maximum 30 minutes after incu bation with KCN and remained elevated up to 60 minutes in both the hip pocampus and cerebellum. Pretreatment with MK-801 and APV, specific NM DA receptor antagonists, blocked the cyanide-stimulated translocation in the hippocampus and cerebellum, whereas CNQX, an AMPA/kainate recep tor antagonist, did not alter the response. These results demonstrate that cyanide stimulates PKC activation and translocation from the cyto sol to membranes in select brain areas and NMDA receptor activation me diates this process.