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.
Jin
Tae-Eun
TE
Abt Zellphysiologie, Max-Planck-Institut für Medizinische Forschung, Heidelberg, Germany.
Wernig
Anton
A
Witzemann
Veit
V
D000818:Animals; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009045:Motor Endplate / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D018995:Myosin Heavy Chains / Q000032:analysis / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D018995:Myosin Heavy Chains