scholarly journals The dynamics of recycled acetylcholine receptors at the neuromuscular junction in vivo

Development ◽  
2006 ◽  
Vol 133 (22) ◽  
pp. 4485-4493 ◽  
Author(s):  
E. G. Bruneau ◽  
M. Akaaboune
Keyword(s):  
Neuromuscular Junction ◽  
Acetylcholine Receptors

scholarly journals Processing of ARIA and release from isolated nerve terminals

1999 ◽  
Vol 354 (1381) ◽  
pp. 411-416 ◽  
Author(s):  
Bomie Han ◽  
Gerald D. Fischbach
Keyword(s):  
Neuromuscular Junction ◽  
Action Potential ◽  
Acetylcholine Receptors ◽  
Molecular Layer ◽  
Postsynaptic Membrane ◽  
High Density ◽  
Small Contribution ◽  
Presynaptic Nerve Terminal ◽  
Voltage Gated

The neuromuscular junction is a specialized synapse in that every action potential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a single presynaptic input makes only a small contribution to the population postsynaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage–gated Na + channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action potential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage–gated Na + channels in cultured myotubes, probably plays the same roles at developing and mature motor endplates in vivo . ARIA is synthesized as part of a larger, transmembrane, precursor protein called proARIA. Delivery of ARIA from motor neuron cell bodies in the spinal cord to the target endplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractions containing synaptosomes from the chick cerebellum as a model system.

scholarly journals In vivo recovery of muscle contraction after alpha-bungarotoxin binding.

1975 ◽  
Vol 66 (1) ◽  
pp. 209-213 ◽  
Author(s):  
H C Fertuck ◽  
W Woodward ◽  
M M Salpeter
Keyword(s):  
Fine Structure ◽  
Neuromuscular Junction ◽  
Muscle Contraction ◽  
Acetylcholine Receptors ◽  
Actinomycin D ◽  
Recovery Period ◽  
Em Autoradiography ◽  
Alpha Bungarotoxin ◽  
In Vivo Recovery

Acetylcholine receptors were inactivated in vivo at the mouse neuromuscular junction using alpha-bungarotoxin (alpha-BTX). It was found that neurally produced muscle contraction recovered within 4-8 days (halftime similar to 3 days). Actinomycin D interfered with this recovery, but did not affect normal nerve-stimulated muscle contraction. If the response was initially eliminated by [125-I]alpha-BTX and the end plates examined by EM autoradiography, no evidence of mass internalization of bound radioactivity during recovery was seen. The fine structure of the end plates and muscle was unaltered during the post-alpha-BTX recovery period.

scholarly journals Regulation of the Rapsyn Promoter by Kaiso and δ-Catenin

2004 ◽  
Vol 24 (16) ◽  
pp. 7188-7196 ◽  
Author(s):  
Marianna Rodova ◽  
Kevin F. Kelly ◽  
Michael VanSaun ◽  
Juliet M. Daniel ◽  
Michael J. Werle
Keyword(s):  
Transcription Factor ◽  
Neuromuscular Junction ◽  
Acetylcholine Receptors ◽  
Consensus Sequence ◽  
Specific Protein ◽  
C2c12 Cells ◽  
Congenital Myasthenic Syndrome ◽  
P120 Catenin ◽  
Myasthenic Syndrome

ABSTRACT Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that δ-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and δ-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and δ-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and δ-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, δ-catenin, and myogenic transcription factors at the neuromuscular junction.

scholarly journals Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In Vivo

2010 ◽  
Vol 104 (5) ◽  
pp. 2352-2358 ◽  
Author(s):  
Xueyong Wang ◽  
Qingbo Wang ◽  
Kathrin L. Engisch ◽  
Mark M. Rich
Keyword(s):  
Neuromuscular Junction ◽  
Muscle Activity ◽  
Acetylcholine Receptors ◽  
Quantal Content ◽  
Spontaneous Release ◽  
Postsynaptic Activity ◽  
Activity Dependent

Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of α-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release ( p), whereas BTX-induced blockade increased the number of releasable vesicles ( n). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n. We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n.

scholarly journals Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site.

1995 ◽  
Vol 128 (4) ◽  
pp. 625-636 ◽  
Author(s):  
M Gesemann ◽  
A J Denzer ◽  
M A Ruegg
Keyword(s):  
Amino Acids ◽  
Alternative Splicing ◽  
Neuromuscular Junction ◽  
Motor Neurons ◽  
Active Site ◽  
Acetylcholine Receptors ◽  
Muscle Cells ◽  
Effective Concentration ◽  
Achr Clustering

Agrin is a basal lamina protein that induces aggregation of acetylcholine receptors (AChRs) and other molecules at the developing neuromuscular junction. Alternative splicing of chick agrin mRNA at two sites, A and B, gives rise to eight possible isoforms of which five are expressed in vivo. Motor neurons express high levels of isoforms with inserts at sites A and B, muscle cells synthesize isoforms that lack amino acids at the B-site. To obtain further insights into the mechanism of agrin-induced AChR aggregation, we have determined the EC50 (effective concentration to induce half-maximal AChR clustering) of each agrin isoform and of truncation mutants. On chick myotubes, EC50 of the COOH-terminal, 95-kD fragment of agrinA4B8 was approximately 35 pM, of agrinA4B19 approximately 110 pM and of agrinA4B11 approximately 5 nM. While some AChR clusters were observed with 64 nM of agrinA4B0, no activity was detected for agrinA0B0. Recombinant full-length chick agrin and a 100-kD fragment of ray agrin showed similar EC50 values. A 45-kD, COOH-terminal fragment of agrinA4B8 retained high activity (EC50 approximately equal to 130 pM) and a 21-kD fragment was still active, but required higher concentrations (EC50 approximately equal to 13 nM). Unlike the 45-kD fragment, the 21-kD fragment neither bound to heparin nor did heparin inhibit its capability to induce AChR aggregation. These data show quantitatively that agrinA4B8 and agrinA4B19, expressed in motor neurons, are most active, while no activity is detected in agrinA0B0, the dominant isoform synthesized by muscle cells. Furthermore, our results show that a fragment comprising site B8 and the most COOH-terminal G-like domain is sufficient for this activity, and that agrin domains required for binding to heparin and those for AChR aggregation are distinct from each other.

scholarly journals A Novel Labeling Approach Identifies Three Stability Levels of Acetylcholine Receptors in the Mouse Neuromuscular Junction In Vivo

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20524 ◽  
Author(s):  
Siegfried Strack ◽  
Yvonne Petersen ◽  
Anika Wagner ◽  
Ira V. Röder ◽  
Marina Albrizio ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Acetylcholine Receptors ◽  
Labeling Approach

Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons

2021 ◽  
pp. 0271678X2110103
Author(s):  
Nao Hatakeyama ◽  
Miyuki Unekawa ◽  
Juri Murata ◽  
Yutaka Tomita ◽  
Norihiro Suzuki ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Acetylcholine Receptors ◽  
Step Function ◽  
Muscarinic Acetylcholine Receptors ◽  
Cell Type ◽  
Function Type ◽  
Neuron Activation ◽  
Cell Type Specific ◽  
Arterial Responses

A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.

MYASTHENIA GRAVIS: A SERUM FACTOR BLOCKING ACETYLCHOLINE RECEPTORS OF THE HUMAN NEUROMUSCULAR JUNCTION

The Lancet ◽  
1975 ◽  
Vol 305 (7907) ◽  
pp. 607-609 ◽  
Author(s):  
AdamN Bender ◽  
W King Engel ◽  
StevenP Ringel ◽  
MathewP Daniels ◽  
Zvi Vogel
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Serum Factor

N-cholinergic facilitation of glutamate release from an individual retinotectal fiber in frog

2001 ◽  
Vol 18 (4) ◽  
pp. 549-558 ◽  
Author(s):  
A. KURAS ◽  
N. GUTMANIENĖ
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Action Potentials ◽  
Acetylcholine Receptors ◽  
Kynurenic Acid ◽  
Glutamate Release ◽  
Synaptic Potentials ◽  
Lower Vertebrates ◽  
Optic Fibers ◽  
Retinotectal Transmission

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.

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