Genetic inactivation of acetylcholinesterase causes functional and structural impairment of mouse soleus muscles.
Acetylcholinesterase (AChE) plays an essential role in neuromuscular transmission. Not surprisingly, neuromuscular transmission during repetitive nerve stimulation is severely depressed in the AChE knockout mouse (KO). However, whether this deficit in AChE leads to skeletal muscle changes is not known. We have studied the in vitro contractile properties of the postural and locomotor soleus muscles of adult KO and normal (wildtype, WT) mice, and this was completed by histological and biochemical analyses. Our results show that muscle weight, cross-sectional area of muscle fibres and absolute maximal isometric force are all reduced in KO mice compared with WT mice. Of interest, the relative amount of slow myosin heavy chain (MHC-1) in muscle homogenates and the percentage of muscle fibres expressing MHC-1 are decreased in the KO mice. Surprisingly, AChE ablation does not modify twitch kinetics, absolute maximal power, fatigue resistance or citrate synthase activity, despite the reduced number of slow muscle fibres. Thus, a deficit in AChE leads to alterations in the structure and function of muscles but these changes are not simply related to the reduced body weight of KO mice. Our results also suggest that this murine model of congenital myasthenic syndrome with endplate AChE deficiency combines alterations in both neurotransmission and intrinsic muscle properties.
INSERM U787, Paris, France.
A
A
Vignaud
F
F
Fougerousse
E
E
Mouisel
N
N
Guerchet
C
C
Hourde
F
F
Bacou
G S
GS
Butler-Browne
A
A
Chatonnet
A
A
Ferry
D000110:Acetylcholinesterase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D000110:Acetylcholinesterase; D018995:Myosin Heavy Chains