title: Low Ca2+ buffering in hypoglossal motoneurons of mutant SOD1 (G93A) mice.
abstract: Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are associated with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by a selective degeneration of brainstem and spinal motoneurons. The pathomechanism of degeneration is still incompletely understood, but includes a disruption in cellular Ca2+ homeostasis. Here we report a quantitative microfluorometric analysis of the Ca2+ homeostasis in vulnerable hypoglossal motoneurons of neonatal mutant (G93A) SOD1 transgenic mice, a mouse model of human ALS. Ca2+ transient decay times (tau = 0.3 s), extrusion rates (gamma = 92 s(-1)) and exceptionally low intrinsic Ca2+ binding ratios (kappaS = 30) were found to be in the same range as compared to non-transgenic animals. Together with the previous observation of high Ca2+ binding ratios in ALS-resistant neurons (e.g. oculomotor), this supports the assumption that low Ca2+ buffering in vulnerable motoneurons represents a significant risk factor for degeneration. On the other hand, alterations in buffering properties by expression of mutant SOD1 are unlikely to be involved in disease initiation.
authors.affiliation: Center for Physiology and Pathophysiology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: von Lewinski
authors.forename: Julia
authors.initials: J
authors.lastname: Fuchs
authors.forename: Bodo K
authors.initials: BK
authors.lastname: Vanselow
authors.forename: Bernhard U
authors.initials: BU
authors.lastname: Keller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology*; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002118:Calcium