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Transfection of N ‐Methyl‐ d ‐Aspartate Receptors in a Nonneuronal Cell Line Leads to Cell Death
Author(s) -
Anegawa Norifusa J.,
Lynch David R.,
Verdoorn Todd A.,
Pritchett Dolan B.
Publication year - 1995
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.1471-4159.1995.64052004.x
Subject(s) - excitotoxicity , nmda receptor , transfection , glutamate receptor , receptor , microbiology and biotechnology , biology , programmed cell death , neurotransmitter receptor , cell culture , neurotransmitter , biochemistry , apoptosis , genetics
Neurons grown in culture die when they are exposed to high concentrations (0.1–1 m M ) of the neurotransmitter l ‐glutamate. A similar phenomenon may occur in the mammalian brain during ischemia and other injuries that cause excessive glutamate release. Activation of N ‐methyl‐ d ‐aspartate (NMDA) receptors and the consequent Ca 2+ influx are thought to play a critical role in the process of neuronal toxicity. Events subsequent to the Ca 2+ influx are not well understood. We have discovered that nonneuronal kidney cells expressing NMDA receptors after DNA transfection undergo cell death unless they are protected by drugs that block the NMDA receptor ion channel. Furthermore, transfected cells expressing a mutated NMDA receptor that conducts less Ca 2+ are less vulnerable to cell death. In addition, we find that even though several active forms of NMDA receptors can be synthesized in these cells after transfection with different cloned subunits, not all receptor types are equally toxic. These experiments suggest that Ca 2+ influx through NMDA channels may be toxic to nonneuronal cells and that the NMDA receptor expression may be the major neuron‐specific component of excitotoxicity.