Nerve terminal ATPase as possible trigger for neurotransmitter release

The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K+-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K+ depolarization, in the presence of Ca2+, triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A–blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca2+ is required for synaptic vesicle membrane retrieval.

Download Full-text

Calcium, Calmodulin, and Synaptic Function: Modulation of Neurotransmitter Release, Nerve Terminal Protein Phosphorylation, and Synaptic Vesicle Morphology by Calcium and Calmodulin

Regulatory Mechanisms of Synaptic Transmission ◽

10.1007/978-1-4684-3968-7_11 ◽

1981 ◽

pp. 205-239 ◽

Cited By ~ 7

Author(s):

Robert J. DeLorenzo

Keyword(s):

Protein Phosphorylation ◽

Synaptic Vesicle ◽

Nerve Terminal ◽

Neurotransmitter Release ◽

Synaptic Function ◽

Terminal Protein

Download Full-text

Presynaptic Proteins as Markers of the Neurotoxic Activity of BmjeTX-I and BmjeTX-II Toxins fromBothrops marajoensis(Marajó Lancehead) Snake Venom

Biochemistry Research International ◽

10.1155/2016/2053459 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10

Author(s):

Antonio Lisboa ◽

Rodolfo Melaré ◽

Junia R. B. Franco ◽

Carolina V. Bis ◽

Marta Gracia ◽

...

Keyword(s):

Nerve Terminal ◽

Neurotransmitter Release ◽

Acetylcholine Receptors ◽

Motor Nerve ◽

Synaptic Proteins ◽

Muscle Fibres ◽

Motor Nerve Terminal ◽

Transmission Electron ◽

Skeletal Muscle Fibres

Neuromuscular preparations exposed toB. marajoensisvenom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposedin vitroto BmjeTX-I and BmjeTX-II toxins fromB. marajoensisvenom. CBC incubated with toxins showed irreversible twitch tension blockade and unaffected KCl- and ACh-evoked contractures, and the positive colabelling of acetylcholine receptors confirmed that their action was primarily at the motor nerve terminal. Hypercontraction and loose myofilaments and synaptic vesicle depletion and motor nerve damage indicated that the toxins displayed both myotoxic and neurotoxic effect. The blockade resulted from interference on synaptophysin, synaptobrevin, and SNAP25 proteins leading to the conclusion that BmjeTX-I and BmjeTX-II affected neurotransmitter release machinery by preventing the docking of synaptic vesicles to the axolemma of the nerve terminal.

Download Full-text

Presynaptic roles of intracellular Ca2+ stores in signalling and exocytosis

Biochemical Society Transactions ◽

10.1042/bst0380529 ◽

2010 ◽

Vol 38 (2) ◽

pp. 529-535 ◽

Cited By ~ 16

Author(s):

Sohaib Nizami ◽

Vivian W.Y. Lee ◽

Jennifer Davies ◽

Philip Long ◽

Jasmina N. Jovanovic ◽

...

Keyword(s):

Protein Kinases ◽

G Protein ◽

Nerve Terminal ◽

Neurotransmitter Release ◽

Glutamate Release ◽

Neuronal Cells ◽

Receptor Activation ◽

Pivotal Role ◽

Presynaptic Function ◽

G Protein Coupled

The signalling roles of Ca2+ic (intracellular Ca2+) stores are well established in non-neuronal and neuronal cells. In neurons, although Ca2+ic stores have been assigned a pivotal role in postsynaptic responses to Gq-coupled receptors, or secondarily to extracellular Ca2+ influx, the functions of dynamic Ca2+ic stores in presynaptic terminals remain to be fully elucidated. In the present paper, we review some of the recent evidence supporting an involvement of Ca2+ic in presynaptic function, and discuss loci at which this source of Ca2+ may impinge. Nerve terminal preparations provide good models for functionally examining putative Ca2+ic stores under physiological and pathophysiological stimulation paradigms, using Ca2+-dependent activation of resident protein kinases as sensors for fine changes in intracellular Ca2+ levels. We conclude that intraterminal Ca2+ic stores may, directly or indirectly, enhance neurotransmitter release following nerve terminal depolarization and/or G-protein-coupled receptor activation. During conditions that prevail following neuronal ischaemia, increased glutamate release instigated by Ca2+ic store activation may thereby contribute to excitotoxicity and eventual synaptopathy.

Download Full-text

Drugs affecting the central nervous system: Effects of pemoline and tricyclic antidepressants on nerve terminal adenosine triphosphatase activities and neurotransmitter release

Neuropharmacology ◽

10.1016/0028-3908(78)90017-5 ◽

1978 ◽

Vol 17 (6) ◽

pp. 419-421 ◽

Cited By ~ 11

Author(s):

J.C. Gilbert ◽

J.M. Allen ◽

B.G. Townsend ◽

M.G. Wyllie

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nerve Terminal ◽

Neurotransmitter Release ◽

Adenosine Triphosphatase ◽

Tricyclic Antidepressants ◽

The Central Nervous System

Download Full-text

Neurotransmitter Secretion along Growing Nerve Processes: Comparison with Synaptic Vesicle Exocytosis

The Journal of Cell Biology ◽

10.1083/jcb.144.3.507 ◽

1999 ◽

Vol 144 (3) ◽

pp. 507-518 ◽

Cited By ~ 67

Author(s):

Stanislav Zakharenko ◽

Sunghoe Chang ◽

Michael O'Donoghue ◽

Sergey V. Popov

Keyword(s):

Nerve Terminal ◽

Neurotransmitter Release ◽

Synaptic Vesicles ◽

High Frequency Stimulation ◽

Spinal Cord Neurons ◽

Presynaptic Nerve Terminal ◽

Neurotransmitter Secretion ◽

Synaptic Vesicle Exocytosis ◽

Vesicle Exocytosis ◽

Membrane Components

In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.

Download Full-text

Low-frequency Neuromuscular Depression Is a Consequence of a Reduction in Nerve Terminal Ca2+ Currents at Mammalian Motor Nerve Endings

Anesthesiology ◽

10.1097/aln.0b013e31829083d8 ◽

2013 ◽

Vol 119 (2) ◽

pp. 326-334

Author(s):

Eugene M. Silinsky

Keyword(s):

Nerve Terminal ◽

Nerve Stimulation ◽

Neurotransmitter Release ◽

Neuromuscular Junctions ◽

Motor Nerve ◽

Neuromuscular Block ◽

Low Frequency ◽

Neuromuscular Blocking ◽

Train Of Four ◽

Train Of Four Monitoring

Abstract Background: The decline in voluntary muscle contraction during low-frequency nerve stimulation is used clinically to assess the type and degree of neuromuscular block. The mechanism underlying this depression is unknown. Methods: Simultaneous electrophysiological measurements of neurotransmitter release and prejunctional Ca2+ currents were made at mouse neuromuscular junctions to evaluate the hypothesis that decreases in nerve terminal Ca2+ currents are responsible for low-frequency depression. Results: Under conditions generally used to measure Ca2+ currents at the neuromuscular junction, increasing the frequency of nerve stimulation briefly from 0.017 to 0.1–1 Hz caused a simultaneous reduction in the release of the neurotransmitter acetylcholine to 52.2 ± 4.4% of control and the Ca2+ current peak to 75.4 ± 2.0% of control (P < 0.001, n = 5 experiments for both measurements, mean ± SEM for all data). In conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter release declined to 42.0 ± 1.0% of control and the Ca2+ current peak declined to 75.8 ± 3.3% of control between the first and fourth stimulus (P < 0.001, n = 7 experiments for both measurements). Depression in acetylcholine release during train-of-four protocols also occurred in the absence of neuromuscular-blocking drugs. Discussion: The results demonstrate that neuromuscular depression during train-of-four monitoring is due to a decline in nerve terminal Ca2+ currents, hence reducing the release of acetylcholine. As similar processes may come into play at higher stimulation frequencies, agents that antagonize the decline in Ca2+ currents could be used to treat conditions in which neuromuscular depression can be debilitating.

Download Full-text

Bretylium abolishes neurotransmitter release without necessarily abolishing the nerve terminal action potential in sympathetic terminals

British Journal of Pharmacology ◽

10.1038/sj.bjp.0707623 ◽

2008 ◽

Vol 153 (4) ◽

pp. 831-839 ◽

Cited By ~ 6

Author(s):

K L Brain ◽

T C Cunnane

Keyword(s):

Action Potential ◽

Nerve Terminal ◽

Neurotransmitter Release

Download Full-text

Synapsins and Synaptic Transmission

Physiology ◽

10.1152/physiologyonline.1993.8.1.18 ◽

1993 ◽

Vol 8 (1) ◽

pp. 18-23

Author(s):

F Benfenati ◽

F Valtorta

Keyword(s):

Synaptic Transmission ◽

Nerve Terminal ◽

Neurotransmitter Release ◽

Synaptic Vesicles ◽

Cytoskeletal Proteins ◽

Nerve Terminals ◽

Short Term ◽

Cytoplasmic Side

The synapsins are a family of nerve terminal-specific phosphoproteins associated with the cytoplasmic side of synaptic vesicles that interact with various cytoskeletal proteins in a phosporylation-dependent fashion. They are implicated in the short-term regulation of neurotransmitter release and in the maturation of developing nerve terminals during synaptogenesis.

Download Full-text