ACTIVATION OF ALPHA(7) NICOTINIC ACETYLCHOLINE-RECEPTOR PROMOTES SURVIVAL OF SPINAL-CORD MOTONEURONS

Spinal cord motoneurons (MNs) undergo a process of cell death during e mbryonic development [1] and are the target of lethal acquired or inhe rited disorders, such as the amyotrophic lateral sclerosis, Therefore, the identification of mechanisms leading to MN survival is of crucial importance, Elevations in intracellular Ca2+ promote chicken MN survi val during the embryonic period of naturally occurring cell death [2,3 ]. We have recently demonstrated that the alpha(7) nicotinic acetylcho line receptor (nAChR) mediates significant increases in free Ca2+ conc entration at membrane potentials at which other pathways for Ca2+ infl ux are inactive [4,5], Although it is possible that Ca2+ influx throug h eel nAChR promotes cell survival, the relation between alpha(7) nACh R activation, cytosolic free Ca2+ and mammalian spinal cord MN surviva l has not been established, In the present study we have now demonstra ted that Ca2+ influx through the alpha(7)-subunit is sufficient to res cue a significant number of cultured spinal cord MNs from programmed c ell death induced by trophic factor deprivation. This is the first dem onstration that neuronal nAChRs are involved in the regulation of MN s urvival. (C) 1997 Federation of European Biochemical Societies.