Published May 18, 2023
| Version v1
Publication
Altered Intracellular Ca2+ Homeostasis in Nerve Terminals of Severe Spinal Muscular Atrophy Mice
Description
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 Ca 2 during repetitive stimulation. Together, these results show
that the reduction of SMN affects synaptic maturation, evoked release, and regulation of intraterminal Ca 2 levels.
Additional details
Identifiers
- URL
- https://idus.us.es/handle//11441/146357
- URN
- urn:oai:idus.us.es:11441/146357