TRANSIENT DISRUPTION OF NERVE-MUSCLE INTERACTION SHORTLY AFTER BIRTH PERMANENTLY ALTERS THE DEVELOPMENT OF THE RAT SOLEUS MUSCLE

Transient paralysis of the rat soleus muscle shortly after birth leads to a permanent loss of motoneurones as revealed by retrograde labelli ng, Mere we show that this loss of motoneurones is reflected in a redu ction in the number of motor units. Soleus muscles in normal adult rat s were found to have 27 (+/-0.6 S.E.M., n = 9) motor units. However, i n muscles which had been treated with alpha-bungarotoxin (BTX) at birt h and 3 days of age, causing paralysis lasting for 6-8 days, only 15 ( +/-0.6 S.E.M., n = 5) motor units remain. The effects of paralysis on the ability of the adult soleus muscle to develop force was also teste d. Following treatment with a single BTX implant at birth, causing par alysis for 2-3 days, soleus muscles develop less tension(73.7% +/- 4.5 S.E.M., n = 8) and weigh less (88.2% +/- 3.8 S.E.M., n = 13) than the ir unoperated controls. This loss of muscle force is caused by a loss of muscle fibres, which in muscles that had been paralysed at birth wa s 81.4% (+/-4.1 S.E.M., n = 5) of control. Prolonging the duration of paralysis led to a greater reduction in force production, weight and t he number of muscle fibres. Those muscles which had been paralysed at birth also took longer to relax during single twitch contractions. In addition, whereas normal soleus muscles contain around 20% of muscle f ibres that do not react with antibodies to slow myosin HC, in soleus m uscles paralysed at birth, 100% of the fibres reacted with this antibo dy. This study shows that disruption of neuromuscular interaction Tor a brief period after birth leads to a loss of motoneurones and a perma nent impairment of muscle function.