Cortical neurones with Ca2+ permeable AMPA/kainate channels display distinct receptor immunoreactivity and are GABAergic.
A minority subset of cortical neurones exhibit kainate-activated Co2+ uptake, a marker for AMPA/kainate receptor gated Ca2+-permeable channels. Consistent with enhanced Ca2+ influx through these channels, Co2+-positive neurones are unusually vulnerable to death induced by exposure to either AMPA or kainate. Here we show that Co2+-positive cortical neurones express a distinctive profile of AMPA receptor subunits as determined by immunostaining. Co2+-positive neurones were much less likely to express GluR2/GluR3, and much more likely to express GluR1 or GluR4, than the general cortical neuronal population. Thus expression of AMPA receptors lacking the GluR2 subunit may explain the Co2+ staining, and selective vulnerability to kainate exhibited by Co2+-positive cells. Almost all GABAergic neurones, identified by immunostaining for glutamic acid decarboxylase, were Co2+-positive. The widespread presence of Ca2+-permeable AMPA/kainate receptor-gated channels on cortical GABAergic neurones may have important implications for the fate of cortical inhibition in disease states associated with the excitotoxic overstimulation of glutamate receptors.
Yin
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Department of Neurology, University of California Irvine, Irvine, California 92717-4290, USA.
Turetsky
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D
Choi
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DW
Weiss
J H
JH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000502:physiology*; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid