Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.
Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally.
Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain.
Josep
J
Tomàs
Manel M
MM
Santafé
Neus
N
Garcia
Maria A
MA
Lanuza
Marta
M
Tomàs
Núria
N
Besalduch
Teresa
T
Obis
Mercedes
M
Priego
Erica
E
Hurtado
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D009469:Neuromuscular Junction / Q000166:cytology* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D055366:Synaptic Potentials / Q000502:physiology
D017978:Receptors, Growth Factor; D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; D000109:Acetylcholine
cytokine receptors; muscarinic receptors; neurotransmission; neurotrophin receptors; purinergic receptors