Changes in motor end-plates resulting from muscle fibre necrosis and regeneration

Duchen, L. W.; Excell, Barbara J.; Patel, Rickesh N.; Smith, Betty

doi:10.1016/0022-510x(74)90041-0

Cited by 70 publications

(23 citation statements)

References 18 publications

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“…However, we find that individual junctions of both phenotypes undergo rapid, abrupt changes. The changes in these synapses mirror those that occur upon deliberate damage to the postsynaptic muscle fiber (Duchen et al, 1974; Couteaux et al, 1988; Rich and Lichtman, 1989; Li and Thompson, 2011). The AChR at these junctions rapidly disappear as the muscle fiber underneath them undergoes necrosis.…”

Section: Introductionmentioning

confidence: 68%

Changes in Aging Mouse Neuromuscular Junctions Are Explained by Degeneration and Regeneration of Muscle Fiber Segments at the Synapse

Lee²,

2011

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Vertebrate neuromuscular junctions are highly stable synapses, retaining the morphology they achieve in early postnatal development throughout most of life. However, these synapses undergo dramatic change during aging. The acetylcholine receptors (AChRs) change from smooth gutters into fragmented islands and the nerve terminals change similarly to be varicosities apposed to these islands. These changes have been attributed to a slow deterioration in mechanisms maintaining the synapse. We have utilized repeated, vital imaging to investigate how these changes occur in the sternomastoid muscle of aging mice. We have found, contrary to expectation, that individual junctions change infrequently, but change, when it occurs, is sudden and dramatic. The change mimics that reported previously for cases in which muscle fibers are deliberately damaged: most of the AChR present disappear rapidly and are replaced by a new set of receptors that become fragmented. The fiber segment underneath the synapse has centrally located nuclei, showing that this segment has undergone necrosis, quickly regenerated, and been reinnervated with an altered synapse. We show that necrotic events are common in aged muscle and have likely been missed previously as a cause of the alterations in aging because central nuclei are a transient phenomenon and the necrotic events at the junction infrequent. However, the changes are permanent and accumulate over time. Interventions to reduce the neuromuscular changes during aging should likely focus on making muscle fibers resistant to injury.

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Section: Introductionmentioning

confidence: 68%

Changes in Aging Mouse Neuromuscular Junctions Are Explained by Degeneration and Regeneration of Muscle Fiber Segments at the Synapse

Lee²,

2011

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“…They further reported that the anes thetic drug bupivacaine had a specific myotoxic effect but no deleterious effect on nerve fibers on the basis of their findings of intact axons and end-plate cholinesterase in necrotic muscle 1 day after bupivacaine injection. Duchen et al [1974] had also reported that axons remained normal despite muscle fiber degeneration 1 day after injection of cardiotoxin. These facts suggest that muscle degeneration due to anesthetic drugs does not always result in neuronal dysfunction, at least in the short term.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Degeneration of Muscle Spindles in the Masseter Muscle after Treatment of Developing Mice with the Local Anesthetic Lidocaine Hydrochloride

Maeda

Osawa²,

Masuda³

et al. 1989

Cells Tissues Organs

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The effect of lidocaine-HCl on muscle spindles in the masseter muscle of developing mice was investigated. Repeated injections of mice with anesthetic in the short term decreased the diameters of primary endings, intrafusal muscle fibers and outer capsules in the equatorial regions of muscle spindles, and caused a drop in the succinic dehydrogenase activity in intrafusal muscle fibers of the muscle spindles. In addition, the diameters did not recover to the control value even after about 10 weeks following cessation of anesthetic treatment. Thus, the present results suggest that repeated use of lidocaine-HCl in developing animals may cause dysfunction of the skeletal muscles.

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“…The animals were allowed to survive for 72 h then, under ether anaesthesia, fixation was started by the perfusion of formolcalcium through the left ventricle. The whole limb was subsequently decalcified, and the two blocks cut from the calf region were prepared for embedding in wax (Duchen, Excell, Patel & Smith, 1974). Transverse sections were stained with haematoxylin and eosin.…”

Section: Perfused Rat Heartmentioning

confidence: 99%

“…Transverse sections were stained with haematoxylin and eosin. At 72 h, necrotic fibres are easily visualized due to extensive cellular infiltration (Duchen et al, 1974). Post-mortem examination was carried out in the majority of mice which were killed at the stage of either partial or full intoxication following intravenous or subcutaneous injection of Mojave toxin.…”

Section: Perfused Rat Heartmentioning

confidence: 99%

Sites of Action of Mojave Toxin Isolated From the Venom of the Mojave Rattlesnake

Gopalakrishnakone

Hawgood

Holbrooke

et al. 1980

British J Pharmacology

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1 Mojave toxin isolated from the venom of the Mojave rattlesnake (Crotalus scutulatus scutulatus) produced an irreversible blockade of the contractile response of the mouse hemidiaphragm to stimulation of the phrenic nerve in vitro, at concentrations of 0.16 to 20 pig/ml; the response to direct stimulation was not affected over a testing period of several hours.2 Mojave toxin (1 to 4 ptg/g) was injected into the tail vein of mice and the intoxicated hemidiaphragm preparation was removed either for testing the contractile response or for intracellular recording. 3 In fully intoxicated hemidiaphragms the contractile response to indirect stimulation was either small and transient or absent, whilst the response to direct stimulation was well maintained. 4 Intracellular recording showed that resting membrane potentials of the muscle fibres were within the normal range. Endplates were difficult to locate but miniature endplate potentials (m.e.p.ps) were recorded at sites at which neurally evoked responses either could not be detected or did not exceed 2 mV which corresponds to transmitter release of a few quanta only. 5 The mean frequency of m.e.p.ps at fully intoxicated endplates was not significantly different from controls but potassium depolarization produced only a small increase in m.e.p.p. frequency relative to the control response. A 50 Hz tetanus had no effect on m.e.p.p. frequency.6 When a sub-lethal dose (3 pg) of Mojave toxin was injected into one hindlimb of mice and the tissues examined at 72 h, there was histological evidence of myonecrosis.7 The isolated perfused heart of the rat was exposed to recycled Mojave toxin (50 and 100 pg/ml) but showed no change in rate or force of ventricular contraction. 8 Post-mortem examination of intoxicated mice showed a frequent incidence of localized areas of interstitial and intra-alveolar haemorrhage in the lungs. Other organs including skin and muscle were not affected. 9 Mojave toxin showed antigenic similarities to crotoxin, the lethal neurotoxin in the venom of the South American rattlesnake, as determined by the ability of antiserum raised against crotoxin to neutralize Mojave toxin. 10 With systemic Mojave intoxication of rapid onset, the cause of death was respiratory paralysis. However, the toxin acts at multiple sites at differing rates of action. With a slower rate of intoxication, impaired respiration may act synergistically with cardiovascular changes to produce circulatory failure. The desirability of using an antivenin with a high titre against Mojave toxin is indicated.

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Changes in motor end-plates resulting from muscle fibre necrosis and regeneration

Cited by 70 publications

References 18 publications

Changes in Aging Mouse Neuromuscular Junctions Are Explained by Degeneration and Regeneration of Muscle Fiber Segments at the Synapse

Changes in Aging Mouse Neuromuscular Junctions Are Explained by Degeneration and Regeneration of Muscle Fiber Segments at the Synapse

Prolonged Degeneration of Muscle Spindles in the Masseter Muscle after Treatment of Developing Mice with the Local Anesthetic Lidocaine Hydrochloride

Sites of Action of Mojave Toxin Isolated From the Venom of the Mojave Rattlesnake

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