Sympathetic innervation in skeletal muscle and its role at the neuromuscular junction

Abstract

Neuromuscular junctions are the synapses between motor neurons and skeletal muscle fibers, which mediate voluntary muscle movement. Since neuromuscular junctions are also tightly associated with the capping function of terminal Schwann cells, these synapses have been classically regarded as tripartite chemical synapses. Although evidences from sympathetic innervation of neuromuscular junctions was described approximately a century ago, the essential presence and functional relevance of sympathetic contribution to the maintenance and modulation of neuromuscular junctions was demonstrated only recently. These findings shed light on the pathophysiology of different clinical conditions and can optimize surgical and clinical treatment modalities for skeletal muscle disorders.

Keywords: Acetylcholine receptor; Adrenoceptor; Neuromuscular junction; Sympathetic.

Fig. 1

Sympathetic nervous system acts upon multiple targets within skeletal muscle tissue. The schematic drawing illustrates that sympathetic innervation in skeletal muscle as a functional unit affects not only vasomotor activity, but impacts also on muscle fiber and motor neuron physiology, e.g., by controlling muscle force production and synchrony of synaptic vesicle (SV) release, respectively. At the NMJ postsynapse, sympathetic release of norepinephrine (NE) affects the protein turnover in general and that of nicotinic acetylcholine receptors (nAChR), in particular. Mechanistically, this appears to involve downregulation of proteolytic systems (atrogenes, calpain). Control of these systems might occur via adrenoceptor-mediated tuning of cAMP/PKA and/or HDAC4/myogenin axes. In addition, sympathetic innervation positively affects PGC-1alpha signaling