Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain.
J Neurosci. 2010 Jan 20;30(3):849-57. doi: 10.1523/JNEUROSCI.4496-09.2010.
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 approximately 55%. In addition, asynchronous release is increased approximately 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.
运动神经元存活数（SMN）蛋白水平低会导致脊髓性肌萎缩症（SMA），这是一种严重的遗传性疾病，其特征为运动功能障碍和过早死亡。虽然 SMN 是一种普遍存在的蛋白，但运动神经元比其他细胞更容易受到 SMN 水平低的影响。为了深入了解 SMA 的发病机制，我们比较了不同年龄和两个近端肌肉中野生型和严重 SMA 小鼠运动终板的突触功能。我们的结果表明，突变肌纤维能正常发放动作电位，且多神经末梢是功能性的。通过研究神经末梢内突触传递的三个主要成分（自发性、诱发和非同步释放）的特征，我们发现，突触后电位的动力学变慢，诱发神经递质释放减少约 55%。此外，非同步释放增加约 300%，表明在重复刺激过程中，细胞内钙离子异常增加。综上所述，这些结果表明，SMN 的减少会影响突触成熟、诱发释放和细胞内钙离子水平的调节。
