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Expression of functional α7 nicotinic acetylcholine receptor during mammalian muscle development and denervation

Authors

  • Uwe Fischer,

    1. Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55099 Mainz, Germany
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  • Sigrid Reinhardt,

    1. Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55099 Mainz, Germany
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  • Edson X. Albuquerque,

    1. Department of Pharmacology and Experimental Therapeutics, University of Maryland Medical School, Baltimore, MD 21201, USA
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  • Alfred Maelicke

    1. Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55099 Mainz, Germany
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: Professor Alfred Maelicke, as above.
E-mail: alfred.maelicke@uni-mainz.de

Abstract

We have studied, on the transcriptional, protein and functional level, the expression of α7 nicotinic acetylcholine receptors (nAChR) in the course of rat muscle development, denervation and renervation. At foetal day 13, α7 nAChR expression was observed in somites and developing muscles of the back, but not yet in migrating myoblasts. Two days later, concomitant with myoblast aggregation, the α7 isoform began to be expressed in isolated myoblasts, with the highest level of expression in the frontal zone of the migrating wave. On foetal day 18, a time when the myoblasts in the upper hindleg have fused, α7 nAChR expression was most prominent in the outer layer of muscle tissue. The highest level of expression was observed in the first postnatal week, when practically all muscle cells stained positively for α7 protein. During the following weeks, α7 nAChR expression slowly decreased and practically disappeared in adult hindleg muscle. Following chronic denervation of adult Soleus muscle fibres, expression of α7 nAChR returned within 2–4 weeks.

Electrophysiological measurements showed that the α7 nAChR of chronically denervated soleus muscle fibres were functional and, in particular, that they could be activated by choline. The presence of the α7 nAChR in developing and denervated muscle suggests a role for this nicotinic receptor in neuronal pathfinding and/or endplate stabilization.

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