• Annalisa Bernareggi, Marina Sciancalepore, and Paola Lorenzon.
• Department of Life Sciences, University of Trieste, Trieste, Italy; B.R.A.I.N., Centre for Neuroscience, Trieste, Italy. Electronic address: abernareggi@units.it.
• Neuroscience. 2020 Jul 15; 439: 41-47.

AbstractSince 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. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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