Interplay Between Cholinergic and Adenosinergic Systems in Skeletal Muscle

Since the pioneering works of Ricardo Miledi, the neuromuscular junction represents the best example of a synapse where ACh is the neurotransmitter acting on nicotinic ACh receptors. ATP, co-released with ACh, is promptly degraded to Ado, which acts as a modulator of the cholinergic synaptic activity. Consequently, both ACh and adenosine play a crucial role in controlling the nerve-muscle communication. Apart from their role in the context of synaptic transmission, ACh and adenosine are autocrinally released by skeletal muscle cells, suggesting also a non nerve-driven function of these molecules. Indeed, the existence of cholinergic and adenosinergic systems has been widely described in many other non neuronal cell types. In this review, we will describe the two systems and their interplay in non-innervated differentiating skeletal muscle cells, and in innervated adult skeletal muscle fibers. We believe that the better comprehension of the interactions between the activity of nAChRs and adenosine could help the knowledge of skeletal muscle physiology.