Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals

• Autores: Pagani, M.R.; Reisin, R.C.; Uchitel, O.D.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: J. Neurosci. 2006;26(10):2661-2672
• Materia: Calcium channels; Calcium homeostasis alteration; IP3R; Phospholipase C; RyR; Signaling mechanisms; calcium; calcium channel N type; calcium ion; immunoglobulin G; inositol trisphosphate; neurotransmitter; phospholipase C; proteinase; ryanodine receptor; adult; aged; amyotrophic lateral sclerosis; animal tissue; antigen antibody reaction; article; autoimmunity; calcium signaling; calcium transport; clinical article; controlled study; degenerative disease; enzyme activity; human; immune response; immunoreactivity; male; motoneuron; mouse; nerve ending; neuromodulation; neurotransmitter release; nonhuman; presynaptic membrane; priority journal; receptor upregulation; synaptic potential; synaptic transmission; Adult; Aged; Amyotrophic Lateral Sclerosis; Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Channels, N-Type; Calcium Signaling; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Enzyme Inhibitors; Evoked Potentials; Female; Humans; Immunoglobulin G; Immunohistochemistry; Immunoprecipitation; Inositol 1,4,5-Trisphosphate Receptors; Male; Mice; Middle Aged; Muscle Fibers; Neuromuscular Junction; Neurotransmitter Agents; omega-Conotoxin GVIA; Phospholipase C; Presynaptic Terminals; Receptors, Cytoplasmic and Nuclear; Ryanodine Receptor Calcium Release Channel; Statistics; Synaptic Transmission; Time Factors
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underlying mechanisms are unknown. Here we showed that IgG purified from a group of sporadic ALS patients, but not familial ALS patients, specifically interact with the presynaptic membrane of motoneurons through an antigen-antibody interaction and modulated synaptic transmission. Immunoreactivity against nerve terminals showed strong correlation with synaptic modulation ability. In addition, several controls have ruled out the possibility for this synaptic modulation to be mediated through proteases or nonspecific effects. Effective IgG potentiated both spontaneous and asynchronous transmitter release. Application of pharmacological inhibitors suggested that activation of this increased release required a nonconstitutive Ca2+ influx through N-type (Ca v2.2) channels and phospholipase C activity and that activation of IP3 and ryanodine receptors were necessary to both activate and sustain the increased release. Consistent with the notion that ALS is heterogeneous disorder, our results reveal that, in ∼50% of ALS patients, motor nerve terminals constitutes a target for autoimmune response. Copyright © 2006 Society for Neuroscience.
Fil:Pagani, M.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.