Different receptors mediate motor neuron death induced by short and long exposures to excitotoxicity

We compared the effect of short and long exposures of cultured motor neuron s to glutamate and kainate (KA) and studied the receptors involved in these two types of excitotoxicity. There was no difference in the receptor type used between short and long glutamate exposures as activation of the N-meth yl-D-asparate (NMDA) receptor was in both cases responsible for the motor n euron death. Cell death through activation of alpha -amino-3-hydroxy-5-meth yl-4-isoxazole propionic acid (AMPA) receptors only became apparent when de sensitization of these receptors was prevented. In such conditions, motor n eurons became much more sensitive to excitotoxicity, and activation of diff erent types of AMPA receptors mediated motor neuron death after short, comp ared to long, exposures to the non-desensitizing AMPA receptor agonist, KA. Short KA exposures selectively affected motor neurons containing Ca2+-perm eable AMPA receptors, as the KA effect was completely inhibited by Joro spi der toxin and only motor neurons that were positive for the histochemical C o2+ staining were killed. A long exposure to KA affected motor neurons thro ugh both Ca2+-permeable and Ca2+-impermeable AMPA receptors. The selective death of motor neurons vs. dorsal horn neurons was observed after short KA exposures indicating that the selective vulnerability of motor neurons to e xcitotoxicity is related to the presence of Ca2+-permeable AMPA receptors. (C) 2000 Elsevier Science Inc.