Characterization of neuromuscular transmission in mice with progressive motoneuronopathy

Progressive motoneuronopathy (PMN) is an autosomal recessive mouse disease, which is characterized by the development of hind limbs paralysis rapidly progressing to the anterior parts of the body, muscular atrophy, respiratory depression, and death at 6-7 postnatal weeks. Here, we recorded the resting membrane potential (RMP), spontaneous miniature endplate potentials (MEPPs), and quantum content of endplate potentials (EPP) at the diaphragm muscle fibers in controls and PMN mice aged 18 to 43 days. In control animals, there was a progressive increase in RMP, MEPP frequency and EPP quantum content, as well as a decrease in mean MEPP amplitude. In PMN mice, the developmental increase in frequency and decrease in the amplitude of MEPPs was practically stopped at the postnatal day 18, whereas RMP increased but only until the age of 31 days and then progressively decreased. The distribution histogram of RMP in PMN mice older than 35 days revealed the existence of two subpopulations of muscle fibers: one showing a denervation-like decrease in RMP and the second, which was matching controls. In addition, EPP quantum content was significantly attenuated in older PMN animals. These results indicate that neurotransmission is severely affected in advanced, but not in early stage of disease, which is apparently due to a partial denervation of the muscles.