Neural regulation of acetylcholinesterase‐associated collagen Q in rat skeletal muscles

Abstract

Acetylcholinesterase‐associated collagen Q is expressed also outside of neuromuscular junctions in the slow soleus muscle, but not in fast muscles. We examined the nerve dependence of muscle collagen Q expression and mechanisms responsible for these differences. Denervation decreased extrajunctional collagen Q mRNA levels in the soleus muscles and junctional levels in fast sternomastoid muscles to about one third. Cross‐innervation of denervated soleus muscles by a fast muscle nerve, or electrical stimulation by ‘fast’ impulse pattern, reduced their extrajunctional collagen Q mRNA levels by 70–80%. In contrast, stimulation of fast muscles by ‘slow’ impulse pattern had no effect on collagen Q expression. Calcineurin inhibitors tacrolimus and cyclosporin A decreased collagen Q mRNA levels in the soleus muscles to about 35%, but did not affect collagen Q expression in denervated soleus muscles or the junctional expression in fast muscles. Therefore, high extrajunctional expression of collagen Q in the soleus muscle is maintained by its tonic nerve‐induced activation pattern via the activated Ca2+‐calcineurin signaling pathway. The extrajunctional collagen Q expression in fast muscles is independent of muscle activation pattern and seems irreversibly suppressed. The junctional expression of collagen Q in fast muscles is partly nerve‐dependent, but does not encompass the Ca2+‐calcineurin signaling pathway.

Zonisamide Enhances Neurite Elongation of Primary Motor Neurons and Facilitates Peripheral Nerve Regeneration In Vitro and in a Mouse Model

“…Eight weeks after surgery, histological and morphometric analyses of cross sections of tibialis anterior muscle showed that zonisamide accelerated recovery from denervation atrophy ( Fig 6F and 6G ). In addition, gene expression of Chrne [ 28 ], Colq [ 29 ], and Rapsn [ 30 ], which are specifically expressed at the neuromuscular junction, were increased in zonisamide-treated mice ( Fig 6H ). We also examined gene expression in a sciatic nerve segment distal to the distal transected site ( S3 Fig ).…”

Dissociation of Transcription, Translation, and Assembly of Collagen-tailed Acetylcholinesterase in Skeletal Muscle

“…The regulation of mammalian ColQ has been studied during differentiation of the C2/C12 mouse muscle cell line in culture (16,17) and in differentiated adult rat muscle in vivo (15,18,19) with emphasis on the transcriptional control elements responsible for muscle-type-specific expression. However, all these studies measured enzyme activity and/or transcript levels rather than the actual ColQ protein.…”