SPINAL-CORD NEURONS ARE VULNERABLE TO RAPIDLY TRIGGERED KAINATE NEUROTOXICITY IN-VITRO

Initial studies found glutamate injury to murine spinal cultures (14-1 7 days in vitro) to reflect contributions of both NMDA and AMPA/kainat e receptors. Subsequent experiments found the spinal cultures to be mo re sensitive than cortical cultures to injury from prolonged low level kainate exposures, and, unlike cortical cultures, to be significantly damaged by relatively brief (30-60 min) kainate exposures. This rapid ly triggered kainate damage to spinal neurons is Ca2+-dependent. Also. more than 40% of spinal neurons (in comparison to about 15% of cortic al neurons) are subject to kainate-activated Co2+ uptake (Co2+(+) neur ons), a histochemical technique that labels neurons with Ca2+-permeabl e AMPA/kainate channels. These spinal Co2+(+) neurons are very sensiti ve to Ca2+-dependent kainate injury, and show greater kainate-induced elevations in intracellular Ca2+ concentrations ([Ca2+](i)) than other spinal neurons during low level kainate exposures. Thus, the heighten ed vulnerability of spinal neurons to kainate toxicity may at least in part reflect the large proportion that possess Ca2+ permeable AMPA/ka inate channels, permitting receptor activation to trigger rapid Ca2+ i nflux and overwhelm the cells Ca2+ homeostatic capabilities.