Aim: 

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) acts as a master pacemaker that controls circadian rhythms of behavior and metabolism and synchronizes the circadian clocks in peripheral tissues. In skeletal muscle, the SCN has a double role, as it entrains both the muscle cell-autonomous circadian clock and the circadian rhythm of locomotor activity. However, it is not known whether motor activity and muscle clock gene rhythms are coupled together and controlled by the same entrainment signals.

Methods: 

We have examined the role of neural and nonneural signals in circadian activity and clock gene expression patterns in skeletal muscle, focusing on core clock genes Bmal1, Per1 and Per2, and NFAT transcription factors, which are known to act as activity sensors.

Results and conclusions: 

Here we show that NFATs show circadian variations in nucleocytoplasmic shuttling and transcriptional activity, which are abrogated by denervation. In contrast, clock gene expression is independent of activity, as denervation did not significantly alter the phase of core clock gene expression. However, a restricted feeding schedule phase-shifted Bmal1 expression in skeletal muscle, as in liver and heart, and cyclic Per1 and Per2 expression in skeletal muscle exhibited a blunted amplitude, showing that the core muscle clock relies on blood-borne and not neural signals. Microarray analyses on innervated and denervated muscles identified the presence of both activity-dependent and -independent circadian rhythms of gene expression in skeletal muscle.