Adrenergic Modulation of Acetylcholine Release at the Mouse Neuromuscular Junctions of Fast-Twitch Skeletal Muscle.

The sympathoadrenal system functions as an adaptive and trophic system, ensuring increased vitality in humans and animals. Recent findings suggest that, in addition to its effects on muscle tissue, neuromuscular junctions (NMJs) may represent an important target for action of sympathetic mediators. Here, we presented experimental data on neurotransmitter release modulation by adrenergic ligands at the NMJs of mouse fast-twitch skeletal muscle levator auris longus. Adrenaline (but not noradrenaline) increased both spontaneous and evoked acetylcholine (ACh) release. This effect of adrenaline was accompanied by an increase in action potential-elicited Ca2+ entry into motor nerve terminals. Blockage of adenylate cyclase and protein kinase A (but not Na, K-ATPase) prevented the facilitatory effect of adrenaline on ACh release. Sympathetic nerves as well as immunoexpression of α1-, α2- and β1-, β2-adrenoceptors (ARs) were revealed in close proximity to the NMJs. Agonists of α2- and β1-ARs had no marked presynaptic effects. α1-AR activation reduced spontaneous and evoked ACh release in a phospholipase A2 and protein kinase C-dependent manner. Effects of β2-AR activation were dependent on the type of agonist: Procaterol decreased both ACh release and Ca2+ entry into the nerve terminals, whereas fenoterol promoted ACh release in a Gi protein-dependent manner. Thus, synaptic transmission in the "fast" NMJs had specific features of adrenergic regulation engaging Gi protein, adenylyl cyclase, phospholipase A2, protein kinases A and C. The positive effect of natural agonist adrenaline was reproduced only by β2-AR activation with fenoterol, but not α1-, α2-, β1-agonists and β2-agonist procaterol.