The blockage of motor impulses in an asynchronized volley at the neuromuscular junction

Dun, F. T.

doi:10.1002/jcp.1030460212

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…amplitude monitored with external electrodes progressively fatigued to plateau at 5-10% of initial amplitude . Intracellular recordings insured that this fatigue was due to a reduction in the amount of transmitter released from all end plates, not to a complete cessation of release from certain end plates which would have occurred if they had failed to conduct the nerve impulse at 10/s (20,51) .…”

Section: Appearance After 15 Min Of Stimulationmentioning

confidence: 99%

Evidence for Recycling of Synaptic Vesicle Membrane During Transmitter Release at the Frog Neuromuscular Junction

Heuser

Reese

1973

The Journal of Cell Biology

2,030

1,279

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When the nerves of isolated frog sartorius muscles were stimulated at 10 Hz, synaptic vesicles in the motor nerve terminals became transiently depleted . This depletion apparently resulted from a redistribution rather than disappearance of synaptic vesicle membrane, since the total amount of membrane comprising these nerve terminals remained constant during stimulation . At 1 min of stimulation, the 30 0/0 depletion in synaptic vesicle membrane was nearly balanced by an increase in plasma membrane, suggesting that vesicle membrane rapidly moved to the surface as it might if vesicles released their content of transmitter by exocytosis . After 15 min of stimulation, the 607, depletion of synaptic vesicle membrane was largely balanced by the appearance of numerous irregular membrane-walled cisternae inside the terminals, suggesting that vesicle membrane was retrieved from the surface as cisternae . When muscles were rested after 15 min of stimulation, cisternae disappeared and synaptic vesicles reappeared, suggesting that cisternae divided to form new synaptic vesicles so that the original vesicle membrane was now recycled into new synaptic vesicles . When muscles were soaked in horseradish peroxidase (HRP), this tracer first entered the cisternae which formed during stimulation and then entered a large proportion of the synaptic vesicles which reappeared during rest, strengthening the idea that synaptic vesicle membrane added to the surface was retrieved as cisternae which subsequently divided to form new vesicles . When muscles containing HRP in synaptic vesicles were washed to remove extracellular HRP and restimulated, HRP disappeared from vesicles without appearing in the new cisternae formed during the second stimulation, confirming that a one-way recycling of synaptic membrane, from the surface through cisternae to new vesicles, was occurring . Coated vesicles apparently represented the actual mechanism for retrieval of synaptic vesicle membrane from the plasma membrane, because during nerve stimulation they proliferated at regions of the nerve terminals covered by Schwann processes, took up peroxidase, and appeared in various stages of coalescence with cisternae . In contrast, synaptic vesicles did not appear to return directly from the surface to form cisternae, and cisternae themselves never appeared directly connected to the surface . Thus, during stimulation the intracellular compartments of this synapse change shape and take up extracellular protein in a manner which indicates that synaptic vesicle membrane added to the surface during exocytosis is retrieved by coated vesicles and recycled into new synaptic vesicles by way of intermediate cisternae .

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Section: Appearance After 15 Min Of Stimulationmentioning

confidence: 99%

Evidence for Recycling of Synaptic Vesicle Membrane During Transmitter Release at the Frog Neuromuscular Junction

Heuser

Reese

1973

The Journal of Cell Biology

2,030

1,279

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“…Presynaptic failure There are very few references in the literature to the kind of presynaptic failure which has been described in this paper. Dun (1955a) seems to be the only author to have suggested that there may be failure of conduction in the fine motor nerve terminals in normal muscles, albeit on the basis of rather unsubstantial evidence. Brooks (1954) thought that botulinum toxin probably blocks conduction in the fine branches close to the nerve endings, but more recently (Brooks, 1956) he has rejected this suggestion.…”

mentioning

confidence: 99%

Presynaptic failure of neuromuscular propagation in rats

Krnjević¹,

Miledi²

1959

The Journal of Physiology

287

167

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“…Such a fivefold increase in extracellular calcium is known to increase transmitter output about twofold (8), but it is not such a high level of calcium that one need worry about it's blocking the conduction of action potentials into the nerve terminal during prolonged repetitive stimulation (25) . Nevertheless, to be sure to avoid any problem with conduction block, we chose to deliver stimuli in intermittent bursts of -40 stimuli delivered over 1 .5 s (i .e ., -25 Hz), alternating with 1 .5-s periods of rest, for the entire 5 min of stimulation (10). With this paradigm chosen (5 min of interrupted 25 Hz stimulation in 10 mM calcium), several normal muscles were stimulated and prepared for examination by freeze substitution .…”

mentioning

confidence: 99%

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

Hirokawa¹,

Heuser²

1981

The Journal of Cell Biology

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Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five times more calcium than normal. Applying this same stimulation paradigm to botulinumintoxicated nerves produced no mitochondrial changes at all . Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium . These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization-evoked calcium currents that accompany nerve activity . Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes .

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The blockage of motor impulses in an asynchronized volley at the neuromuscular junction

Cited by 4 publications

References 7 publications

Evidence for Recycling of Synaptic Vesicle Membrane During Transmitter Release at the Frog Neuromuscular Junction

Evidence for Recycling of Synaptic Vesicle Membrane During Transmitter Release at the Frog Neuromuscular Junction

Presynaptic failure of neuromuscular propagation in rats

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

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