Neuronal involvement in muscular atrophy.

The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, dec novo expression of hemichannels formed by connexins and other none selective channels, including P2X7 receptors, TRPV2 channels were demonstrated in denervated fast skeletal muscles. Denervated muscles presented activation of the transcription factor NF-kB and increase mRNA levels of proinflammatory cytokines, indicating activation of the inflammasome. Moreover, the denervation-induced atrophy and activation of the inflammasome were drastically prevented in denervated muscles deficient in connexins 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned none selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., BDNF), agrin/Lrp4/MuSK and acetylcholine are among the possible perpetrators of repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression. [ABSTRACT FROM AUTHOR]