Reorganization of synaptic inputs to developing skeletal muscle fibres.

During early stages of postnatal development skeletal muscle fibres of mammals are contacted by several axons. The transition from poly- to mononeuronal innervation has been extensively studied on the rat soleus. The role of activity in this process has been acknowledged but the mechanisms leading to synapse remodelling are not understood. The participation of the muscle has to be taken into account; if muscles are paralysed by alpha-bungarotoxin, the elimination of terminals is arrested. Changes in Ca2+ also influence the rate of removal of terminals. Calcium seems to act through a calcium-activated neutral protease (CANP) present in nerve endings. If CANP is inhibited, elimination fails to take place. Thus Ca2+ enters the terminal and activates the CANP. Release of K+ ions from active muscle could link muscle activity and synapse elimination. Excess K+ was found to reduce nerve-muscle contacts, by depolarizing terminals and allowing Ca2+ entry. A greater increase of Ca2+ concentration in smaller terminals would be expected, because of their surface-to-volume ratio, and they are preferentially eliminated. Thus elimination depends on the unequal size of terminals at the endplate. Therefore the 'survivability' of individual nerve endings may already be determined at the time of synapse elimination.