title: Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels' activation in a genetic model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by a substantial loss of motor neurons in the spinal cord, brain stem and motor cortex. By combining electrophysiological recordings with imaging techniques, clearance/buffering capacity of cultured spinal cord motor neurons after a calcium accumulation has been analyzed in response to AMPA receptors' (AMPARs') activation and to depolarizing stimuli in a genetic mouse model of ALS (G93A). Our studies demonstrate that the amplitude of the calcium signal in response to AMPARs' or voltage-dependent calcium channels' activation is not significantly different in controls and G93A motor neurons. On the contrary, in G93A motor neurons, the [Ca(2+)](i) recovery to basal level is significantly slower compared to control neurons following AMPARs but not voltage-dependent calcium channels' activation. This difference was not observed in G93A cultured cortical neurons. This observation is the first to indicate a specific alteration of the calcium clearance linked to AMPA receptors' activation in G93A motor neurons and the involvement of AMPA receptor regulatory proteins controlling both AMPA receptor functionality and the sequence of events connected to them.
authors: Fondazione S. Lucia, Centro Europeo Ricerca sul Cervello, Via del Fosso di Fiorano, 00173 Roma, Italy.
authors: Ezia
authors: E
authors: Guatteo
authors: Irene
authors: I
authors: Carunchio
authors: Massimo
authors: M
authors: Pieri
authors: Federica
authors: F
authors: Albo
authors: Nadia
authors: N
authors: Canu
authors: Nicola B
authors: NB
authors: Mercuri
authors: Cristina
authors: C
authors: Zona
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008920:Misonidazole / Q000031:analogs & derivatives; D009046:Motor Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D015220:Calcium Channels; D018091:Receptors, AMPA; C031843:fluoromisonidazole; D008920:Misonidazole; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002118:Calcium