MOTOR-NEURONS ARE SELECTIVELY VULNERABLE TO AMPA KAINATE RECEPTOR-MEDIATED INJURY IN-VITRO/

The nonphosphorylated neurofilament marker SMI-32 stains motor neurons in spinal cord slices and stains a subset of cultured spinal neurons [''large SMI-32(+) neurons''], which have a morphology consistent with motor neurons identified in vitro: large cell body, long axon, and ex tensive dendritic arborization. They are found preferentially in ventr al spinal cord cultures, providing further evidence that large SMI-32( +) neurons are indeed motor neurons, and SMI-32 staining often colocal izes with established motor neuron markers (including acetylcholine, c alcitonin gene-related peptide, and peripherin). Additionally, choline acetyltransferase activity (a frequently used index of the motor neur on population) and peripherin(+) neurons share with large SMI-32(+) ne urons an unusual vulnerability to AMPA/kainate receptor-mediated injur y. Kainate-induced loss of these motor neuron markers is Ca2+-dependen t, which supports a critical role of Ca2+ ions in this injury. Raising extracellular Ca2+ exacerbates injury, whereas removal of extracellul ar Ca2+ is protective. A basis for this vulnerability is provided by t he observation that most peripherin(+) neurons, like large SMI-32(+) n eurons, are subject to kainate-stimulated Co2+ uptake, a histochemical stain that identifies neurons possessing Ca2+-permeable AMPA/kainate receptor-gated channels. Finally, of possibly greater relevance to the slow motor neuronal degeneration in diseases, both large SMI-32(+) ne urons and peripherin(+) neurons are selectively damaged by prolonged ( 24 hr) low-level exposures to kainate (10 mu M) or to the glutamate re uptake blocker L-trans-pyrrolidine-2,4-dicarboxylic acid (100 mu M). D uring these low-level kainate exposures, large SMI-32(+) neurons showe d higher intracellular Ca2+ concentrations than most spinal neurons, s uggesting that Ca2+ ions are also important in this more slowly evolvi ng injury.