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In vivo acetylcholine receptor expression induced by calcitonin gene-related peptide in rat soleus muscle
We applied calcitonin gene-related peptide (CGRP) by continuous perfusion of the extrajunctional surface of the adult rat soleus muscle in vivo. We obtained this through a fine polyethylene catheter connected to an Alzet pump implanted in the animal. The perfusion induced a local acetylcholine receptor accumulation in the membrane of the muscle fibres starting with a delay of one to two days, provided a chronic conduction block of soleus innervation was concomitantly present. The effect was prominent, being higher than that following denervation. The lack of acetylcholine receptor accumulation observed in sham perfused animals and the co-administration of CGRP and its competitive antagonist peptide, hCGRP(8-37), eliminates the possibility that the response to CGRP application represents an inflammatory reaction to foreign bodies instead of a specific effect of the peptide.We suggest that CGRP may act on the extrajunctional membrane of muscle fibres to help induce acetylcholine receptor accumulation after appropriate receptors for the peptide are re-expressed due to muscle paralysis. Whilst this is compatible with a role of CGRP in synaptogenesis, a recent study showed that alpha-CGRP(-/-) mutant mice have normal neuromuscular junction development. However, given the redundancy of factors involved in acetylcholine receptor accumulation, further experiments on multiple knock-outs need to be performed before a final conclusion is reached about the physiological significance of CGRP
Paralysis of innervated and reinnervated muscles equally affects contractile properties as does permanent denervation
The effects of long lasting (4--5 weeks) nerve conduction block and denervation were compared by investigating contractile, morphological and histochemical properties of slow (soleus) and fast (EDL) rat skeletal muscles. The block was based on improved perfusion techniques of the sciatic nerve with a tetrodotoxin (TTX) solution delivered at doses adequate to obtain maximal effects in the muscles. The TTX-inactivated axons retained normal histological and physiological properties such as the ability to evoke full contractile responses, to regenerate, and to completely reinnervate muscle. In spite of their intact innervation or of their full reinnervation, the TTX-paralysed muscles underwent weight loss, fibre atrophy and reduction in force output quantitatively indistinguishable from those following denervation. The same was true for all other contractile parameters tested, that is, twitch speed, twitch to tetanus ratio, post-tetanic potentiation, endurance, and fibre type composition. The results indicate the fundamental role of activity as a regulatory signal for muscle contractile properties, while they do not support the notion of a participation of chemical, activity-independent factors in this regulatio
Effects of reinnervation with normal and tetrodotoxin-inactive nerves on resting membrane potential of rat skeletal muscle
Resting membrane potentials (RMPs) have been recorded in vitro near the end-plate region of rat soleus muscles reinnervated with tetrodotoxin-inactive nerves and compared with those of denervated muscles whose reinnervation had been prevented. The two muscle groups exhibited the same low values of RMP typical of denervated muscles. In control muscles of rats in which impulse conduction was left unimpaired, reinnervation induced the expected increase in RMP values towards normal. It is suggested that, at least for this property, reinnervation restores to normal the muscle fibre membrane essentially through the return of activity
Effects of reinnervation upon electrical membrane properties of normal and paralyzed muscles
Resting membrane potentials (RMP) and resistance to tetrodotoxin (TTX) have been compared in denervated rat soleus muscles and muscles reinnervated with tetrodotoxin-inactive nerves for periods of 15-18 days. RMP's of the two muscle groups exhibited the same low values typical of denervated muscles. Similarly, comparable values of TTX-resistance were found in the two muscle groups, although exceptions with slightly lower values in the innervated-paralyzed muscles were noted. It is concluded that muscle reinnervation restores to normal the membrane properties altered by denervation essentially through the return of muscle activity
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