scholarly journals Activation of neuronal nicotinic receptors inhibits acetylcholine release in the neuromuscular junction by increasing Ca2+ flux through Cav1 channels

2021 ◽  
Author(s):  
Nikita Zhilyakov ◽  
Arsenii Arkhipov ◽  
Artem Malomouzh ◽  
Dmitry Samigullin
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Calcium Influx ◽  
Motor Nerve ◽  
Calcium Transient ◽  
Motor Nerve Terminal ◽  
Stable Form ◽  
Ach Release ◽  
Presynaptic Calcium ◽  
Ach Receptors

Background and Purpose: Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system (PNS) and in several branches of the central nervous system (CNS). Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is relationship between nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. Experimental Approach: The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse. ACh release was assessed by electrophysiological methods. Changes in the calcium transients were recorded using a calcium-sensitive dye. Functional interaction between nicotinic ACh receptors and calcium channels was investigated pharmacologically using specific agonists and antagonists. Key Results: Nicotine hydrogen tartrate salt (considered as a stable form for potential therapeutic delivery of nicotine) effects on the parameters of ACh release from the nerve ending were analyzed. Nicotine application (10 μM) decrease the amount of evoked ACh release, while calcium transient increase in the motor nerve terminal. Both of these effects of nicotine were abolished by the neuronal ACh receptor antagonist dihydro-beta-erythroidine and Cav1 blockers, verapamil and nitrendipine. Conclusion and Implications: Neuronal nicotinic ACh receptors activation decreases the number of ACh quanta released by boosting calcium influx through Cav1 channels. Understanding of mechanisms of autoregulation of ACh release is important for the searching new approaches treat diseases associated with cholinergic dysfunction.

scholarly journals Activation of Neuronal Nicotinic Receptors Inhibits Acetylcholine Release in the Neuromuscular Junction by Increasing Ca2+ Flux through Cav1 Channels

2021 ◽  
Vol 22 (16) ◽  
pp. 9031
Author(s):  
Nikita Zhilyakov ◽  
Arsenii Arkhipov ◽  
Artem Malomouzh ◽  
Dmitry Samigullin
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Calcium Influx ◽  
Motor Nerve ◽  
Calcium Transient ◽  
Receptor Activation ◽  
Motor Nerve Terminal ◽  
Ach Release ◽  
Neuronal Nicotinic Receptors ◽  
Presynaptic Calcium

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse. ACh release was assessed by electrophysiological methods. Changes in calcium transients were recorded using a calcium-sensitive dye. Nicotine hydrogen tartrate salt application (10 μM) decreased the amount of evoked ACh release, while the calcium transient increased in the motor nerve terminal. Both of these effects of nicotine were abolished by the neuronal ACh receptor antagonist dihydro-beta-erythroidine and Cav1 blockers, verapamil, and nitrendipine. These data allow us to suggest that neuronal nicotinic ACh receptor activation decreases the number of ACh quanta released by boosting calcium influx through Cav1 channels.

scholarly journals Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

scholarly journals Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves.

1986 ◽  
Vol 103 (2) ◽  
pp. 521-534 ◽  
Author(s):  
J D Black ◽  
J O Dolly
Keyword(s):  
Plasma Membrane ◽  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Motor Nerve ◽  
Type A ◽  
Nerve Trunk ◽  
Metabolic Inhibitors ◽  
Motor Nerve Terminal ◽  
Electron Microscopic Autoradiography

The labeling patterns produced by radioiodinated botulinum neurotoxin (125I-BoNT) types A and B at the vertebrate neuromuscular junction were investigated using electron microscopic autoradiography. The data obtained allow the following conclusions to be made. 125I-BoNT type A, applied in vivo or in vitro to mouse diaphragm or frog cutaneous pectoris muscle, interacts saturably with the motor nerve terminal only; silver grains occur on the plasma membrane, within the synaptic bouton, and in the axoplasm of the nerve trunk, suggesting internalization and retrograde intra-axonal transport of toxin or fragments thereof. 125I-BoNT type B, applied in vitro to the murine neuromuscular junction, interacts likewise with the motor nerve terminal except that a lower proportion of internalized radioactivity is seen. This result is reconcilable with the similar, but not identical, pharmacological action of these toxin types. The saturability of labeling in each case suggested the involvement of acceptors; on preventing the internalization step with metabolic inhibitors, their precise location became apparent. They were found on all unmyelinated areas of the nerve terminal membrane, including the preterminal axon and the synaptic bouton. Although 125I-BoNT type A interacts specifically with developing terminals of newborn rats, the unmyelinated plasma membrane of the nerve trunk is not labeled, indicating that the acceptors are unique components restricted to the nerve terminal area. BoNT types A and B have distinct acceptors on the terminal membrane. Having optimized the conditions for saturation of these binding sites and calibrated the autoradiographic procedure, we found the densities of the acceptors for types A and B to be approximately 150 and 630/micron 2 of membrane, respectively. It is proposed that these membrane acceptors target BoNT to the nerve terminal and mediate its delivery to an intracellular site, thus contributing to the toxin's selective inhibitory action on neurotransmitter release.

Presynaptic Ca2+ Influx at the Inhibitor of the Crayfish Neuromuscular Junction: A Photometric Study at a High Time Resolution

2000 ◽  
Vol 83 (1) ◽  
pp. 552-562 ◽  
Author(s):  
Andrey Vyshedskiy ◽  
Jen-Wei Lin
Keyword(s):  
Action Potential ◽  
Time Resolution ◽  
Transmitter Release ◽  
Calcium Influx ◽  
Calcium Transient ◽  
High Time ◽  
High Time Resolution ◽  
Presynaptic Calcium ◽  
Crayfish Neuromuscular Junction ◽  
Fluorescence Transients

Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us to correlate presynaptic calcium influx with transmitter release at a high time resolution. Systematic testing of the calcium indicators showed that only low-affinity dyes, with affinities in the range of micromolar, should be used to avoid saturation of dye binding and interference with transmitter release. Presynaptic calcium influx was regulated by slowly increasing the duration of the action potential through progressive block of potassium channels. The amplitude of the calcium transient, measured from a cluster of varicosities, was linearly related to the duration of the action potential with a slope of 1.2. Gradual changes in potassium channel block allowed us to estimate the calcium cooperativity of transmitter release over a 10-fold range in presynaptic calcium influx. Calcium cooperativity measured here exhibited one component with an average value of 3.1. Inspection of simultaneously recorded presynaptic calcium transients and inhibitory postsynaptic currents (IPSCs) showed that prolonged action potentials were associated with a slow rising phase of presynaptic calcium transients, which were matched by a slow rate of rise of IPSCs. The close correlation suggests that fluorescence transients provide information on the rate of calcium influx. Because there is an anatomic mismatch between the presynaptic calcium transient, measured from a cluster of varicosities, and IPSC, measured with two-electrode voltage clamp, macropatch recording was used to monitor inhibitory postsynaptic responses from the same cluster of varicosities from which the calcium transient was measured. Inhibitory postsynaptic responses recorded with the macropatch method exhibited a faster rising phase than that recorded with two-electrode voltage clamp. This difference could be attributed to slight asynchrony of transmitter release due to action potential conduction along fine branches. In conclusion, this report shows that fluorescence transients generated by calcium-sensitive dyes can provide insights to the properties of presynaptic calcium influx, and its correlation with transmitter release, at a high time resolution.

scholarly journals Modulation of the vesicle code transmitting the visual signal in the retina

2020 ◽  
Author(s):  
José Moya-Díaz ◽  
Ben James ◽  
Leon Lagnado
Keyword(s):  
Substance P ◽  
Visual Information ◽  
Calcium Influx ◽  
Calcium Transient ◽  
Bipolar Cells ◽  
Visual Signals ◽  
Visual Signal ◽  
Temporal Precision ◽  
Low Pass ◽  
Presynaptic Calcium

SummaryMultivesicular release (MVR) allows retinal bipolar cells to transmit visual signals as changes in both the rate and amplitude of synaptic events. How do neuromodulators reguate this vesicle code? By imaging larval zebrafish, we find that the variability of calcium influx is a major source of synaptic noise. Dopamine increases synaptic gain up to 15-fold while Substance P reduces it 7-fold, both by acting on the presynaptic calcium transient to alter the distribution of amplitudes of multivesicular events. An increase in gain is accompanied by a decrease in the temporal precision of transmission and a reduction in the efficiency with which vesicles transfer visual information. The decrease in gain caused by Substance P was also associated with a shift in temporal filtering from band-pass to low-pass. This study demonstrates how neuromodulators act on the synaptic transformation of the visual signal to alter the way information is coded with vesicles.

Steroid anaesthetics: inhibition of depolarization–secretion coupling at the mouse motor nerve terminal

1980 ◽  
Vol 58 (10) ◽  
pp. 1221-1228 ◽  
Author(s):  
P. Pennefather ◽  
E. Puil ◽  
D. M. J. Quastel
Keyword(s):  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Motor Nerve ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Potassium Depolarization ◽  
End Plate

The coupling between nerve terminal depolarization and quantal secretion of acetylcholine at the mouse neuromuscular junction was estimated by measuring the multiplication of the frequency of miniature end-plate potentials (m.e.p.p.s) produced by increasing the concentration of calcium in the medium from 0.1 to 1.0 mM in the presence of 15 mM potassium. Depolarization–secretion coupling was inhibited by the anaesthetic steroids progesterone, pregnanedione, and alphaxalone. The nonanaesthetic steroid Δ16-alphaxalone also inhibited depolarization–secretion coupling with the same potency as alphaxalone. This result indicates that inhibition of depolarization–secretion coupling in nerve terminals is unlikely to play a major role in the production of anaesthesia.

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