Stabilisation of neuromuscular junctions by leupeptin increases motor unit size in partially denervated rat muscles.

The effect on inhibiting the calcium activated neutral protease (CANP) by leupeptin on force output and motor unit size of the partially denervated rat EDL muscle was studied. Partial denervation was performed under anaesthesia by section of the L4 ventral ramus in 3- and 18-day-old Wistar rats. Two days after the operation a silicon strip containing the inhibitor of CANP leupeptin was implanted alongside the partially denervated EDL. Two to 3 months later the animals were anaesthetized and the EDL muscles on both sides prepared for tension recording. The results from these recordings show dramatic reduction in force output and muscle weight in animals operated at 3 days and this reduction was less pronounced in muscles treated with leupeptin. The mean force output of individual motor units increases in the leupeptin-treated partially denervated muscle compared to the untreated muscle. The increased fatigue resistance typical of muscles partially denervated at 3 days [37] is less pronounced in the treated muscle. In animals operated at 18 days the individual motor units actually increased in size and the leupeptin treatment had no effect on the partially denervated EDL muscles. The difference between the response to leupeptin of the 3 day and 18 day operated animals could be due to the different patterns of innervation of the muscles at the time of the application of the inhibitor of CANP.