Cortical neurones exhibiting kainate-activated co²⁺ uptake are selectively vulnerable to ampa/kainate receptor-mediated toxicity

Kainate-activated Co²⁺ uptake, a histochemical method that identifies cells bearing Ca²⁺-permeable AMPA/kainate receptors, labels approximately 15% of murine cortical neurones in cell culture. While exposure times exceeding several hours were needed for AMPA or kainate to destroy most cultured cortical neurones, the subpopulation exhibiting kainate-activated Co²⁺ uptake was selectively destroyed after AMPA or kainate exposures of only 10-60 min. No selective loss was seen after exposure to NMDA. Kainate toxicity on Co²⁺ uptake-positive neurones was dependent on extracellular Ca²⁺ concentration, and associated with an increase in intracellular free Ca²⁺ even in the absence of extracellular Na⁺. These results suggest that a distinct subpopulation of cortical neurones expresses AMPA/kainate receptors linked to Ca²⁺-permeable channels, and that this characteristic conveys enhanced vulnerability to kainate-induced, Ca²⁺-mediated, damage.