Metabotropic and ionotropic glutamate receptors mediate the modulation of acetylcholine release at the frog neuromuscular junction

Abstract

There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release. Quisqualate's inhibitory effect did not occur when a blocker of Group I mGlu receptors (LY 367385) or an inhibitor of phospholipase C (U73122) was present. An increase in the degree of synchrony of ACh quantal release, such as that produced by Glu, was obtained after application of N-methyl-D-aspartic acid (NMDA). The presence of Group I mGlu and NMDA receptors in the neuromuscular synapse was confirmed by immunocytochemistry. Thus, the data suggest that both metabotropic Group I mGlu receptors and ionotropic NMDA receptors are present at the neuromuscular synapse of amphibians, and that the activation of these receptors initiates different mechanisms for the regulation of ACh release from motor nerve terminals. © 2016 Wiley Periodicals, Inc.

Repeated transspinal stimulation decreases soleus H-reflex excitability and restores spinal inhibition in human spinal cord injury

“…Therefore, repeated transspinal stimulation at intensities that produces depolarization of motoneurons over multiple segments can potentially have affected persistent inward currents exerted at the somata and dendrites of motoneurons. Possible neuroplasticity mechanisms also include potentiation of group Ia afferents hyperpolarization and changes in the concentration of ion channels at nerve terminals [40,41]. This is supported by the summation of the soleus H reflex and soleus TEP in the surface EMG when both responses are matched to depolarize the same soleus motoneurons, and neural interactions are confined to occur at the peripheral nerve axons based on the timing between the two stimuli [7,11].…”

Glutamate at the Vertebrate Neuromuscular Junction: From Modulation to Neurotransmission

“…This effect is most likely mediated by the activation of presynaptic metabotropic glutamate receptors (mGluRs). In fact, mGluRs are present in nerve endings of NMJ of the adult lizard and frog muscles [12,21]. The presence of mGluR3 and mGluR1a/5 was demonstrated by means of immunofluorescence experiments; in both experimental models, the activation mGluRs reduces the level of spontaneous [12,21] and evoked ACh release [21] (Table 1).…”

“…More recent analyses have shown that GluN1 containing NMDA receptors are present on the postsynaptic membrane of NMJs from slow (soleus), fast (EDL), and mixed (diaphragm) muscles and that they are localized within the depth of the secondary folds [23]. Recently, GluN1 containing NMDA receptors on the postsynaptic membrane of adult frog cutaneous pectoris NMJ were shown [21]. Postsynaptic glutamate receptors are activated by endogenous glutamate at the NMJ upon moderate/high frequency stimulation [24,25] (and references therein).…”

Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

“…Activity-dependent mediators derived from the three cells of the synapse cross the extracellular cleft in all directions to generate signals in target metabotropic receptors. In the NMJ, there are other purinergic receptors apart from AR ( Tsim and Barnard, 2002 ; Todd and Robitaille, 2006 ), several mAChR ( Santafé et al, 2007 , 2009 ; Wright et al, 2009 ; Garcia et al, 2010b ), neurotrophin receptors ( Gonzalez et al, 1999 ; Garcia et al, 2011 ; Santafé et al, 2015 ; Nadal et al, 2016a , b ) cytokine receptors ( Ribchester et al, 1998 ; Wang et al, 2002 ; Garcia et al, 2010a , 2012 ), calcitonin gene-related peptide receptors ( Changeux et al, 1992 ; Lu and Fu, 1995 ; Gaydukov et al, 2016 ), glutamate receptors ( Thomas and Sigrist, 2012 ; Personius et al, 2016 ; Tsentsevitsky et al, 2017 ) and neuregulin receptors ( Loeb, 2003 ; Kummer et al, 2006 ; Simeone et al, 2010 ; Schmidt et al, 2011 ; Wang et al, 2017 ). The way a synapse operates is largely the outcome of the confluence of several signaling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes to modulate transmitter release and the stability of the connection.…”