Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat

1. A study of neuromuscular function in regenerating skeletal muscle fibres in the rat soleus muscle has been made. The muscle fibres were damaged in vivo by the injection of the myotoxic venom component notexin, and then allowed to regenerate spontaneously. 2. Regenerating muscle fibres generated action potentials and contracted following direct intracellular stimulation as early as 4 days after the injection of notexin. 3. Miniature endplate potentials (MEPPs) were recorded at a minority of synapses at 3 days, and from all synapses by 5 days. The mean amplitude of MEPPs in a given fibre was directly proportional to muscle fibre input resistance. 4. Spontaneous transmitter release in the regenerating fibres was relatively insensitive to changes in [K+]0 but the effect of Ruthenium Red on spontaneous release was similar in the regenerating and control muscle fibres. 5. Functional innervation, defined as the ability to generate an indirect action potential, was restored in 97% of fibres by 10 days. The generation of an action potential was always associated with a twitch of the muscle fibre. Those fibres that were unable to generate an action potential usually exhibited a low membrane potential (ca -50 mV). These fibres could generate action potentials if they were hyperpolarized using an intracellular current-passing microelectrode. 6. The quantal content of endplate potentials (EPPs) was estimated from the mean EPP and mean MEPP amplitudes in cut muscle fibre preparations. These estimates suggested that quantal content was low at the earliest stages of regeneration, but increased as the muscle fibres matured and became normal at 10-21 days. 7. During repetitive stimulation at 30 Hz there was a fall in the amplitude of EPPs of 40-45%. The fall was similar in regenerating and control fibres. Conducting synapses never exhibited failure to generate an EPP during the period of high-frequency stimulation.