Changes in acetylcholine receptor function induce shifts in muscle fiber type composition

AChRe) ⁄ ) mice lack e−subunits of the acetylcholine receptor and thus fail to express adult−type receptors. The expression of fetal−type receptors throughout postnatal life alters postsynaptic signal transduction and causes a fast−to−slow fiber type transition, both in slow−twitch soleus muscle and in fast−twitch extensor digitorum longus muscle. In comparison to wildtype muscle, the proportion of type 1 slow fibers is significantly increased (6%), whereas the proportion of fast fibers is reduced (in soleus, type 2A by 12%, and in extensor digitorum longus, type 2B ⁄2D by 10%). The increased levels of troponin Islow transcripts clearly support a fast−to−slow fiber type transition. Shifts of protein and transcript levels are not restricted to ‘myogenic' genes but also affect ‘synaptogenic' genes. Clear increases are observed for acetylcholine receptor a−subunits and the postsynaptically located utrophin. Although the fast−to−slow fiber type transition appears to occur in a coordinated manner in both muscle types, muscle−specific differences are retained. Most prominently, the differential expression level of the synaptic regulator MuSK is significantly lower in extensor digitorum muscle than in soleus muscle. The results show a new quality in muscle plasticity, in that changes in the functional properties of endplate receptors modulate the contractile properties of skeletal muscles. Muscle thus represents a self−matching system that adjusts contractile properties and synaptic function to variable functional demands