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.
Turetsky
D M
DM
Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri, 63110, USA.
Canzoniero
L M
LM
Sensi
S L
SL
Weiss
J H
JH
Goldberg
M P
MP
Choi
D W
DW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003035:Cobalt / Q000493:pharmacokinetics* / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*
D002118:Calcium; D003035:Cobalt; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors