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- Title
Altered Intracellular Ca<sup>2+</sup> Homeostasis in Nerve Terminals of Severe Spinal Muscular Atrophy Mice.
- Authors
Ruiz, Rocío; Casañas, Juan José; Torres-Benito, Laura; Cano, Raquel; Tabares, Lucía
- Abstract
Low levels of survival motor neuron (SMN) protein result in spinal muscular atrophy (SMA), a severe genetic disease characterized by motor impairment and premature lethality. Although SMN is a ubiquitous protein, motor neurons are much more vulnerable to low levels of SMN than other cells. To gain insight into the pathogenesis of SMA, we have compared synaptic function of motor terminals in wild-type and severe SMA mice at different ages and in two proximal muscles. Our results show that mutant muscle fibers fire normal action potentials and that multi-innervated terminals are functional. By studying the characteristics of the three main components of synaptic transmission in nerve terminals (spontaneous, evoked, and asynchronous release), we found that the kinetics of the postsynaptic potentials are slowed and evoked neurotransmitter release is decreased by ~55%. In addition, asynchronous release is increased ~300%, indicating an anomalous augmentation of intraterminal bulk Ca2+ during repetitive stimulation. Together, these results show that the reduction of SMN affects synaptic maturation, evoked release, and regulation of intraterminal Ca2+ levels.
- Subjects
SPINAL muscular atrophy; HOMEOSTASIS; GENETIC disorders; NEURAL transmission; LABORATORY mice; NEUROTRANSMITTERS
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 3, p849
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4496-09.2010