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

AChRepsilon(-/-) mice lack epsilon-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 wild-type 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 I(slow) 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 alpha-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.