Cortical neurones exhibiting kainate-activated Co2+uptake are selectively vulnerable to AMPA/kainate receptor-mediated toxicity

Abstract

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.

Keywords

• AMPA
• Ca2+
• Co2+
• glutamate
• kainate
• neurotoxicity