Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in vitro.
Initial studies found glutamate injury to murine spinal cultures (14-17 days in vitro) to reflect contributions of both NMDA and AMPA/kainate receptors. Subsequent experiments found the spinal cultures to be more 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 rapidly triggered kainate damage to spinal neurons is Ca(2+)-dependent. Also, more than 40% of spinal neurons (in comparison to about 15% of cortical neurons) are subject to kainate-activated Co2+ uptake (Co2+(+) neurons), a histochemical technique that labels neurons with Ca(2+)-permeable AMPA/kainate channels. These spinal Co2+(+) neurons are very sensitive to Ca(2+)-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 heightened vulnerability of spinal neurons to kainate toxicity may at least in part reflect the large proportion that possess Ca2+ permeable AMPA/kainate channels, permitting receptor activation to trigger rapid Ca2+ influx and overwhelm the cells Ca2+ homeostatic capabilities.
Yin
H Z
HZ
Department of Neurology, University of California at Irvine 92717-4290, USA.
Park
D D
DD
Lindsay
A D
AD
Weiss
J H
JH
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D003035:Cobalt / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007091:Image Processing, Computer-Assisted; D015640:Ion Channel Gating / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D003035:Cobalt; D007608:Kainic Acid