The Effect of Inhibiting the Calcium Activated Neutral Protease, on Motor Unit Size after Partial Denervation of the Rat Soleus Muscle.

Rat soleus muscles were partially denervated by removal of the L5 ventral ramus at either 4 - 6 days or 17 - 19 days. Local application of leupeptin, a potent inhibitor of the calcium activated neutral protease to these operated muscles, resulted in a significantly greater maximal tetanic tension and motor unit size, when compared to untreated partially denervated muscles. This was achieved in the 4 - 6 day operated animals by an increased number of terminals and in the 17 - 19 day old animals by increased number of axonal sprouts that maintain contact with muscle fibres. In both groups of operated animals in the leupeptin treated muscles large numbers of motor units were able to maintain or achieve an expanded territory, whilst the size of the largest motor unit did not appear to be increased. It is proposed that leupeptin exerts its effect by inhibiting the degradative action of the neuronal calcium activated neutral protease on the axonal cytoskeleton. Such inhibition may act to prevent or decrease the degradation of cytoskeletal structures in the nerve terminal, and so provide protection for weak terminals at a synapse and growth cones of sprouting axons following partial denervation.