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Kainate‐induced excitotoxicity is dependent upon extracellular potassium concentrations that regulate the activity of AMPA/KA type glutamate receptors
Author(s) -
Ha Byeong Keun,
Vicini Stefano,
Rogers Richard C.,
Bresnahan Jacqueline C.,
Burry Richard W.,
Beattie Michael S.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01203.x
Subject(s) - excitotoxicity , kainate receptor , ampa receptor , glutamate receptor , kainic acid , nmda receptor , ionotropic effect , microbiology and biotechnology , neuroscience , extracellular , receptor , chemistry , biology , biophysics , biochemistry
In addition to well‐known N ‐methyl‐ d ‐aspartate (NMDA) receptor‐mediated excitotoxicity, recent studies suggest that non‐NMDA type ionotropic glutamate receptors are also important mediators of excitotoxic neuronal death, and that their functional expression can be regulated by the cellular environment. In this study, we used cerebellar granule cells (CGCs) in culture to investigate kainate (KA)‐induced excitotoxicity. Although previous reports indicated that KA induces apoptosis of CGCs in culture, no KA‐induced excitotoxic cell death was observed in CGCs treated with KA when cells were maintained in high potassium media (24 m m K + ). In contrast, when mature CGCs were shifted into low potassium media (3 m m K + ), KA produced significant excitotoxicity. In electrophysiological studies, the KA‐induced inward current density was significantly elevated in CGCs shifted into low K + media compared with those maintained in high K + media. Non‐desensitizing aspects of KA currents observed in this study suggest that these responses were mediated by AMPA rather than KA receptors. In immunofluorescence studies, the surface expression of GluR1 subunits increased when mature CGCs were shifted into a low K + environment. This study suggests that KA‐induced excitotoxicity in mature CGCs is dependent upon the extracellular potassium concentration, which modulates functional expression and excitability of AMPA/KA receptors.