scholarly journals Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction

2021 ◽  
Vol 22 (9) ◽  
pp. 4611
Author(s):  
Ellya Bukharaeva ◽  
Venera Khuzakhmetova ◽  
Svetlana Dmitrieva ◽  
Andrei Tsentsevitsky
Keyword(s):  
Neuromuscular Junction ◽  
Neurodegenerative Diseases ◽  
Acetylcholine Receptors ◽  
Molecular Mechanisms ◽  
Acetylcholine Release ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Adrenergic Agents ◽  
Cholinergic Synaptic Transmission

Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.

Spontaneous acetylcholine release in mammalian neuromuscular junctions

1997 ◽  
Vol 273 (6) ◽  
pp. C1835-C1841 ◽  
Author(s):  
Adriana Losavio ◽  
S. Muchnik
Keyword(s):  
Neuromuscular Junction ◽  
Acetylcholine Release ◽  
Neuromuscular Junctions ◽  
The Other ◽  
Nerve Terminals ◽  
Transmitter Secretion ◽  
Other Hand ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Lower Effect

Spontaneous secretion of the neurotransmitter acetylcholine in mammalian neuromuscular synapsis depends on the Ca2+ content of nerve terminals. The Ca2+ electrochemical gradient favors the entry of this cation. We investigated the possible involvement of three voltage-dependent Ca2+ channels (VDCC) (L-, N-, and P/Q-types) on spontaneous transmitter release at the rat neuromuscular junction. Miniature end-plate potential (MEPP) frequency was clearly reduced by 5 μM nifedipine, a blocker of the L-type VDCC, and to a lesser extent by the N-type VDCC blocker, ω-conotoxin GVIA (ω-CgTx, 5 μM). On the other hand, nifedipine and ω-CgTx had no effect on K+-induced transmitter secretion. ω-Agatoxin IVA (100 nM), a P/Q-type VDCC blocker, prevents acetylcholine release induced by K+ depolarization but failed to affect MEPP frequency in basal conditions. These results suggest that in the mammalian neuromuscular junction Ca2+ enters nerve terminals through at least three different channels, two of them (L- and N-types) mainly related to spontaneous acetylcholine release and the other (P/Q-type) mostly involved in depolarization-induced neurotransmitter release. Ca2+-binding molecule-related spontaneous release apparently binds Ca2+ very rapidly and would probably be located very close to Ca2+ channels, since the fast Ca2+ chelator (BAPTA-AM) significantly reduced MEPP frequency, whereas EGTA-AM, exhibiting slower kinetics, had a lower effect. The increase in MEPP frequency induced by exposing the preparation to hypertonic solutions was affected by neither external Ca2+concentration nor L-, N-, and P/Q-type VDCC blockers, indicating that extracellular Ca2+ is not necessary to produce hyperosmotic neurosecretion. On the other hand, MEPP frequency was diminished by BAPTA-AM and EGTA-AM to the same extent, supporting the view that hypertonic response is promoted by “bulk” intracellular Ca2+concentration increases.

The effect of calcium on acetylcholine release from motor nerve terminals

1965 ◽  
Vol 161 (985) ◽  
pp. 496-503 ◽  
Keyword(s):  
Neuromuscular Junction ◽  
Calcium Ions ◽  
Acetylcholine Release ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Transmission Process ◽  
Terminal Axon ◽  
Deficient Medium ◽  
Site Of Action ◽  
Release Of Acetylcholine

The method of external focal recording from the neuromuscular junction has been used to locate the site of action of calcium ions in the transmission process. The muscle is placed in a calcium-deficient medium (which contains magnesium as a substitute), and the effect of localized calcium application from the recording micropipette is studied. Electrophoretic application of calcium is followed within less than 1 s by increased terminal release of acetylcholine, shown by a large increase in the number of quantal components of the end-plate potential. This effect is observed even under conditions when the terminal axon spike diminishes in size during the application of calcium. It is concluded that the action of calcium is concerned directly with the release of the transmitter, and not indirectly—as is sometimes suggested—by facilitating propagation or increasing the amplitude of the terminal nerve spike.

scholarly journals Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber.

1991 ◽  
Vol 115 (3) ◽  
pp. 755-764 ◽  
Author(s):  
L Anglister
Keyword(s):  
Basal Lamina ◽  
Ache Activity ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Synaptic Cleft ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Axon Terminals ◽  
Muscle Nerve ◽  
Almost All

Acetylcholinesterase (AChE) in skeletal muscle is concentrated at neuromuscular junctions, where it is found in the synaptic cleft between muscle and nerve, associated with the synaptic portion of the myofiber basal lamina. This raises the question of whether the synaptic enzyme is produced by muscle, nerve, or both. Studies on denervated and regenerating muscles have shown that myofibers can produce synaptic AChE, and that the motor nerve may play an indirect role, inducing myofibers to produce synaptic AChE. The aim of this study was to determine whether some of the AChE which is known to be made and transported by the motor nerve contributes directly to AChE in the synaptic cleft. Frog muscles were surgically damaged in a way that caused degeneration and permanent removal of all myofibers from their basal lamina sheaths. Concomitantly, AChE activity was irreversibly blocked. Motor axons remained intact, and their terminals persisted at almost all the synaptic sites on the basal lamina in the absence of myofibers. 1 mo after the operation, the innervated sheaths were stained for AChE activity. Despite the absence of myofibers, new AChE appeared in an arborized pattern, characteristic of neuromuscular junctions, and its reaction product was concentrated adjacent to the nerve terminals, obscuring synaptic basal lamina. AChE activity did not appear in the absence of nerve terminals. We concluded therefore, that the newly formed AChE at the synaptic sites had been produced by the persisting axon terminals, indicating that the motor nerve is capable of producing some of the synaptic AChE at neuromuscular junctions. The newly formed AChE remained adherent to basal lamina sheaths after degeneration of the terminals, and was solubilized by collagenase, indicating that the AChE provided by nerve had become incorporated into the basal lamina as at normal neuromuscular junctions.

scholarly journals Interaction between Calcium Chelators and the Activity of P2X7 Receptors in Mouse Motor Synapses

2020 ◽  
Vol 21 (6) ◽  
pp. 2034 ◽  
Author(s):  
Anna Miteva ◽  
Alexander Gaydukov ◽  
Olga Balezina
Keyword(s):  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Control Level ◽  
Nerve Terminals ◽  
Quantal Content ◽  
Ach Release ◽  
P2x7 Receptors ◽  
Motor Nerve Terminals ◽  
Pannexin 1 ◽  
End Plate

The ability of P2X7 receptors to potentiate rhythmically evoked acetylcholine (ACh) release through Ca2+ entry via P2X7 receptors and via L-type voltage-dependent Ca2+ channels (VDCCs) was compared by loading Ca2+ chelators into motor nerve terminals. Neuromuscular preparations of the diaphragms of wild-type (WT) mice and pannexin-1 knockout (Panx1−/−) mice, in which ACh release is potentiated by the disinhibition of the L-type VDCCs upon the activation of P2X7 receptors, were used. Miniature end-plate potentials (MEPPs) and evoked end-plate potentials (EPPs) were recorded when the motor terminals were loaded with slow or fast Ca2+ chelators (EGTA-AM or BAPTA-AM, respectively, 50 μM). In WT and Panx1−/− mice, EGTA-AM did not change either spontaneous or evoked ACh release, while BAPTA-AM inhibited synaptic transmission by suppressing the quantal content of EPPs throughout the course of the short rhythmic train (50 Hz, 1 s). In the motor synapses of either WT or Panx1−/− mice in the presence of BAPTA-AM, the activation of P2X7 receptors by BzATP (30 μM) returned the EPP quantal content to the control level. In the neuromuscular junctions (NMJs) of Panx1−/− mice, EGTA-AM completely prevented the BzATP-induced increase in EPP quantal content. After Panx1−/− NMJs were treated with BAPTA-AM, BzATP lost its ability to enhance the EPP quantal content to above the control level. Nitrendipine (1 μM), an inhibitor of L-type VDCCs, was unable to prevent this BzATP-induced enhancement of EPP quantal content to the control level. We propose that the activation of P2X7 receptors may provide additional Ca2+ entry into motor nerve terminals, which, independent of the modulation of L-type VDCC activity, can partially reduce the buffering capacity of Ca2+ chelators, thereby providing sufficient Ca2+ signals for ACh secretion at the control level. However, the activity of both Ca2+ chelators was sufficient to eliminate Ca2+ entry via L-type VDCCs activated by P2X7 receptors and increase the EPP quantal content in the NMJs of Panx1−/− mice to above the control level.

Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice

1997 ◽  
Vol 83 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Mohamed A. Fahim
Keyword(s):  
Neuromuscular Junction ◽  
Endurance Exercise ◽  
Neuromuscular Junctions ◽  
Safety Margin ◽  
Gluteus Maximus ◽  
Nerve Terminals ◽  
Quantal Content ◽  
Age Related ◽  
Endplate Potentials ◽  
Old Mice

Fahim, Mohamed A. Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice. J. Appl. Physiol. 83(1): 59–66, 1997.—The effect of age and endurance exercise on the physiology and morphology of neuromuscular junctions (NMJ) of gluteus maximus muscle was studied in C57BL/6NNia mice. Mice were exercised, starting at 7 or 25 mo of age, at 28 m/min for 60 min/day, 5 days/wk for 12 wk, on a rodent treadmill. Intracellular recordings of spontaneous miniature endplate potentials (MEPP) and the quantal content of endplate potentials (EPP) were recorded from NMJ of 10- and 28-mo-old control and exercised mice. Endurance exercise resulted in significant increases in MEPP amplitudes (23%), quantal content, and safety margin, and a significant decrease in MEPP frequency of young mice, with no change in resting membrane potential or membrane capacitance. Three months of endurance exercise resulted in an increase in MEPP frequency (41%) and decreases in MEPP amplitudes (15%), quantal content, and safety margin of old mice. Endurance exercise resulted in significantly larger nerve terminals (24%) in young animals, suggesting functional adaptation. Nerve terminals in exercised 28-mo-old mice were smaller than in the corresponding control mice, an indication that exercise minimized age-related nerve terminal elaboration. It is concluded that the different physiological responses of young and old gluteus maximus muscles to endurance exercise parallel their morphological responses. This suggests that the mouse NMJ undergoes a process of physiological and morphological remodeling during aging, and such plasticity could be modulated differently by endurance exercise.

scholarly journals Basal lamina directs acetylcholinesterase accumulation at synaptic sites in regenerating muscle.

1985 ◽  
Vol 101 (3) ◽  
pp. 735-743 ◽  
Author(s):  
L Anglister ◽  
U J McMahan
Keyword(s):  
Plasma Membrane ◽  
Neuromuscular Junction ◽  
Basal Lamina ◽  
Acetylcholine Receptors ◽  
Skeletal Muscles ◽  
Ache Activity ◽  
Neuromuscular Junctions ◽  
Muscle Fibers ◽  
Synaptic Cleft

In skeletal muscles that have been damaged in ways which spare the basal lamina sheaths of the muscle fibers, new myofibers develop within the sheaths and neuromuscular junctions form at the original synaptic sites on them. At the regenerated neuromuscular junctions, as at the original ones, the muscle fibers are characterized by junctional folds and accumulations of acetylcholine receptors and acetylcholinesterase (AChE). The formation of junctional folds and the accumulation of acetylcholine receptors is known to be directed by components of the synaptic portion of the myofiber basal lamina. The aim of this study was to determine whether or not the synaptic basal lamina contains molecules that direct the accumulation of AChE. We crushed frog muscles in a way that caused disintegration and phagocytosis of all cells at the neuromuscular junction, and at the same time, we irreversibly blocked AChE activity. New muscle fibers were allowed to regenerate within the basal lamina sheaths of the original muscle fibers but reinnervation of the muscles was deliberately prevented. We then stained for AChE activity and searched the surface of the new muscle fibers for deposits of enzyme they had produced. Despite the absence of innervation, AChE preferentially accumulated at points where the plasma membrane of the new muscle fibers was apposed to the regions of the basal lamina that had occupied the synaptic cleft at the neuromuscular junctions. We therefore conclude that molecules stably attached to the synaptic portion of myofiber basal lamina direct the accumulation of AChE at the original synaptic sites in regenerating muscle. Additional studies revealed that the AChE was solubilized by collagenase and that it remained adherent to basal lamina sheaths after degeneration of the new myofibers, indicating that it had become incorporated into the basal lamina, as at normal neuromuscular junctions.

scholarly journals Ovalbumin-induced sensitization affects non-quantal acetylcholine release from motor nerve terminals and alters contractility of skeletal muscles in mice

2009 ◽  
Vol 94 (2) ◽  
pp. 264-268 ◽  
Author(s):  
Alexander Y. Teplov ◽  
Sergey N. Grishin ◽  
Marat A. Mukhamedyarov ◽  
Airat U. Ziganshin ◽  
Andrey L. Zefirov ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Acetylcholine Release ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Motor Nerve Terminals ◽  
Quantal Acetylcholine Release
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