Tetanic Facilitation of Neuromuscular Transmission by Adenosine A&lt;sub&gt;2A&lt;/sub&gt; and Muscarinic M&lt;sub&gt;1&lt;/sub&gt; Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters

Castellão-Santana, Lilian Martins; Abiko, Priscila Yumi; Ambiel, Célia Regina; Peixoto, Ana Rita; Noronha‐Matos, José Bernardo; Correia-de-Sá, Paulo; Alves-Do-Prado, Wilson

doi:10.1159/000494058

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…Experimental data suggest that release facilitation by M 1 Rs relies mainly on intracellular Ca 2+ recruitment from inositol 1,4,5-triphosphate (IP 3 )-sensitive stores (Fig. 1 a), being relatively insensitive to blockage of PKC activity [ 101 , 124 – 126 ]. Most likely, α3β2-containing nAChRs may facilitate ACh release either through direct Ca 2+ influx via the nicotinic pore or through indirect focal depolarisation of the nerve terminal membrane [ 4 ].…”

Section: Ado Modulates Cholinergic and Peptidergic Signalling At The Nmjmentioning

confidence: 99%

Purinergic Tuning of the Tripartite Neuromuscular Synapse

2023

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The vertebrate neuromuscular junction (NMJ) is a specialised chemical synapse involved in the transmission of bioelectric signals between a motor neuron and a skeletal muscle fiber, leading to muscle contraction. Typically, the NMJ is a tripartite synapse comprising (a) a presynaptic region represented by the motor nerve ending, (b) a postsynaptic skeletal motor endplate area, and (c) perisynaptic Schwann cells (PSCs) that shield the motor nerve terminal. Increasing evidence points towards the role of PSCs in the maintenance and control of neuromuscular integrity, transmission, and plasticity. Acetylcholine (ACh) is the main neurotransmitter at the vertebrate skeletal NMJ, and its role is fine-tuned by co-released purinergic neuromodulators, like adenosine 5′-triphosphate (ATP) and its metabolite adenosine (ADO). Adenine nucleotides modulate transmitter release and expression of postsynaptic ACh receptors at motor synapses via the activation of P2Y and P2X receptors. Endogenously generated ADO modulates ACh release by acting via co-localised inhibitory A1 and facilitatory A2A receptors on motor nerve terminals, whose tonic activation depends on the neuronal firing pattern and their interplay with cholinergic receptors and neuropeptides. Thus, the concerted action of adenine nucleotides, ADO, and ACh/neuropeptide co-transmitters is paramount to adapting the neuromuscular transmission to the working load under pathological conditions, like Myasthenia gravis. Unravelling these functional complexities prompted us to review our knowledge about the way purines orchestrate neuromuscular transmission and plasticity in light of the tripartite synapse concept, emphasising the often-forgotten role of PSCs in this context.

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Section: Ado Modulates Cholinergic and Peptidergic Signalling At The Nmjmentioning

confidence: 99%

Purinergic Tuning of the Tripartite Neuromuscular Synapse

2023

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“…The generated choline is then re-taken-up into presynaptic cholinergic neurons by high-affinity choline transporter (CHT1) and reused for ACh synthesis to maintain cholinergic neurotransmission. Thus, CHT1 activity is considered the rate-limiting step in subsequent ACh synthesis (Okuda et al, 2000(Okuda et al, , 2012Castellao-Santana et al, 2019;for review: Everitt & Robbins, 1997;Sarter & Parikh, 2005;Bazalakova & Blakely, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum

Muramatsu

Uwada

Chihara

et al. 2021

Journal of Neurochemistry

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Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [ 3 H]choline and subsequent synthesis and release of [ 3 H]ACh were investigated in rat striatal segments. Incubation with [ 3 H]choline elicited efficient uptake via high-affinity choline transporter-1, resulting in accumulation of [ 3 H]choline and [ 3 H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [ 3 H]choline led predominantly to the accumulation of [ 3 H]ACh. Electrical stimulation and KCl depolarization selectively released [ 3 H]ACh but not [ 3 H]choline. [ 3 H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [ 3 H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [ 3 H] ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca 2+ dependent and exhibited slightly different sensitivities to N-and P-type Ca 2+ channel toxins (ω-conotoxin GVIA and ω-agatoxin IVA, respectively) between both stimuli. [ 3 H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction-associated disorders, in addition to inhibition of synaptic cleft AChE.

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Tetanic Facilitation of Neuromuscular Transmission by Adenosine A<sub>2A</sub> and Muscarinic M<sub>1</sub> Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters

Cited by 2 publications

References 52 publications

Purinergic Tuning of the Tripartite Neuromuscular Synapse

Purinergic Tuning of the Tripartite Neuromuscular Synapse

Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum

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