KAINIC ACID-INDUCED EXCITOTOXICITY AND CFOS EXPRESSION IN FIBROBLASTSTRANSFECTED WITH GLUTAMATE-RECEPTOR SUBUNIT, GLUR1

Glutamate receptors participate in the majority of fast excitatory neu rotransmission in the mammalian brain. Excessive excitation of these r eceptors has been linked to neuronal dysfunction and death through a p rocess termed excitotoxicity. In this study we demonstrate that transf ection of a single non-NMDA glutamate receptor subunit, GluR1, into cu ltured fibroblasts is sufficient to confer kainic acid mediated excito toxicity similar to that seen in neuronal cells. Death of transfected cells requires at least 24 h of continuous exposure to kainic acid and can be blocked with a glutamate receptor antagonist. Also, the induct ion of protooncogene cfos transcripts occurs 30 min following kainic a cid administration, and Fos protein accumulated in the nucleus within 90 min. Theses observations suggest that the signaling system(s) requi red to initiate gene expression and kainic acid excitotoxicity from a neuronal ionotropic receptor to the nucleus is present in these nonneu ronal cells. Finally, antibodies prepared to amino acids 185-449 of Gl uR1 are demonstrated to be useful for fluorescence-activated sorting o f live cells transfected with a GluR1 expression vector. This supports the conclusion that this region of the protein is located extracellul arly. (C) 1996 John Wiley & Sons, Inc.