Electrophysiology of the neuromuscular junction of the laminin-2 (merosin) deficient C57 BL/6J dy 2J/dy 2J dystrophic mouse

Abstract

The C57 BL/6J dy 2J/dy 2J dystrophic mouse expresses an abnormal truncated form of the α2 subunit of the protein laminin-2 (or merosin), which is unable to form a stable link between the extracellular matrix and the dystrophin-associated proteins, resulting in muscular dystrophy. Morphological abnormalities of the peripheral nervous system and neuromuscular junction have also been reported. The electrophysiological properties of the neuromuscular junctions of diaphragm, extensor digitorum longus (EDL), and soleus from C57 BL/6J dy 2J/dy 2J mice and controls are described. No evidence for the presence of denervated fibres were found. Mean MEPP amplitudes were significantly increased in EDL and soleus but reduced in the diaphragm from affected mice. Mean MEPP frequencies were raised in all the dy 2J/dy 2J muscles studied. dy 2J/dy 2J muscles were paralysed by low concentrations of μ-conotoxin suggesting that embryonic (tetrodotoxin and μ-conotoxin resistant) sodium channels are not widespread on dy 2J/dy 2J muscle as has previously been reported. EPP latencies were significantly prolonged in the diaphragm and EDL but not soleus from dy 2J/dy 2J mice. Quantal contents were higher in all dy 2J/dy 2J muscles. In the dy 2J/dy 2J diaphragm failures in neurotransmission occurred and a faster rate of rundown of EPPs was apparent. Some changes appear from a direct effect of dystrophy, whilst increased MEPP frequency and quantal content, and failures in neurotransmission indicate neuronal abnormalities.