Ca2+ permeable AMPA/kainate channels permit rapid injurious Ca2+ entry

Small subsets of central neurons possessing Ca2+ permeable AMPA/kainate channels can be identified by a histochemical stain based on kainate-stimulated Co2+ uptake (Co2+(+)neurons) and are unusually vulnerable to AMPA/kainate receptor-mediated injury. Using brief kainate exposures (which selectively destroy Co2+(+) neurons) along with kainate triggered 45Ca2+ influx measurements, we estimate kainate to cause an unusually high rate of Ca2+ influx into Co2+(+) neurons. Also, while fura-2 Ca2+ imaging revealed low (10 microM) kainate exposures to preferentially induce intracellular free Ca2+ ([Ca2+]i) elevations in Co2+(+) neurons, intense (100 microM) kainate exposures used in the 45Ca2+ influx studies triggered comparable [Ca2+]i rises in all neurons. These findings suggest that the exceptional vulnerability of Co2+(+) neurons to AMPA/kainate receptor-mediated injury reflects a high rate of agonist triggered Ca2+ influx, and that [Ca2+]i rises may only poorly reflect influx rate.