The specific aim of this project is to study the effect of hypertrophication (enlargement of muscle fibers) on synaptic transmission at the skeletal neuromuscular junction. Hypertrophication will be defined as an increase in the average fiber size as measured by cross sectional area of the test (right soleus) muscle when compared to the control (left soleus). Specifically, we want to know what mechanisms are used by the nerve and muscle to maintain transmission when the muscle fiber enlarges. The results of these experiments will be interpreted through two models: The genetic determination model, and the safety factor conservation model. Currently, we have successfully induced hypertrophication in rat soleus by hemi-ectomy. Hypertrophication of soleus, which is better suitable for our study, occurs at week 4 and 5 post surgical. Our results indicate that the membrane is modified in order to compensate for the impedance mismatch between small motor nerve and enlarged muscle fiber. When muscle fiber enlarges (hypertrophies) membrane impedance increases. This would have been an effect of maintaining the safety factor for neuromuscular transmitters release. The length constant in enlarged muscle fibers increases. In the future, we will investigate the factors that lead to the increase of input impedance. In dennervated muscles, the input impedance also increases. On the other hand, in muscular dystrophy, the input impedance decreases. In both of these cases, changes in resting membrane chloride conductance are responsible for the changes of membrane properties. If the changes of chloride conductance are responsible for the increase of input impedance in hypertrophied muscle fibers, perhaps, the same mechanisms involved in maintaining the safety factor for neurotransmitter release are also involved in muscle pathology.
