Acetylcholine content and release in denervated or botulinum poisoned rat skeletal muscle

Polak, R. L.; Sellin, Lawrence C.; Thesleff, S.

doi:10.1113/jphysiol.1981.sp013905

Cited by 44 publications

(13 citation statements)

References 23 publications

(26 reference statements)

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“…It is probably much harder to keep adequate paralysis for such long time periods. Secondly, the recent work of Polak, Sellin & Thesleff (1981) Berg & Hall (1975) is that this equality of effect of paralysis occurred in as little as 4 days, whereas we find that even in mice it takes as long as 9 days to achieve this when botulinum toxin is used.…”

Section: Discussionmentioning

confidence: 51%

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice

Brown

Hopkins

Keynes

1982

The Journal of Physiology

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SUMMARY1. The properties of denervated and fully innervated but paralysed soleus and extensor digitorum longus (e.d.l.) muscles were compared in mice.2. Muscles were paralysed by single or repeated injections of botulinum toxin into the right lower leg. Contralateral muscles were denervated at the same time by sciatic nerve section. Muscles were excised 3-20 days later and direct and indirect isometric twitch and tetanic tensions measured in vitro. ACh sensitivity was assessed from isometric contractions to various concentrations of bath-applied ACh perchlorate.3. Denervated muscles as expected from the work of others developed sensitivity to ACh earlier and more rapidly than paralysed muscles. A transient peak of sensitivity was reached after 7 days of denervation in soleus and after 8 days in e.d.l. However 2 days later the sensitivity of muscles fully paralysed to nerve twitch and tetanic stimuli was not significantly different from that of denervated muscles.4. In both e.d.l. and soleus the direct tetanus/twitch ratios declined in paralysed and denervated muscles. The decline was initially more rapid in denervated than paralysed soleus, but the ratios for paralysed and denervated muscles were not significantly different after 10 days in either muscle. By this time there were no differences in the absolute strengths of the paralysed and denervated muscles.5. It is concluded that the ACh sensitivity and dynamic properties of fully paralysed mouse muscles become equal to those of denervated muscles once the acute effects associated with nerve degeneration are past. This result is consistent with the idea that normal neuronal control of extrajunctional mammalian skeletal muscle properties is mediated solely by means of activity.

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Section: Discussionmentioning

confidence: 51%

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice

Brown

Hopkins

Keynes

1982

The Journal of Physiology

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“…After botulinum toxin treatment, evoked release of ACh is virtually abolished, but spontaneous release of ACh is only reduced by about half (Polak et al, 1981). Additionally, in both these cases the sensitivity of the inactive muscle to ACh is probably increased, even in the first few days of block, by the development of extra-junctional ACh receptors (e.g.…”

Section: Discussionmentioning

confidence: 96%

The effect of postsynaptic block on development of the neuromuscular junction in postnatal rats

Duxson

1982

J Neurocytol

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The effects of reduced muscle activity on the ultrastructural development of the rat neuromuscular junction (NMJ) have been studied. Soleus muscles of rats were treated with alpha-bungarotoxin (alpha BTx) in order to produce a postsynaptic block of activity between the ages of 10 and 12 days. Muscles of litter mates were treated with saline over the same period. The development of these control and alpha BTx treated muscles was then compared to that of normal muscles from untreated litter mates. During the period between the tenth and twelfth days after birth, normal soleus NMJs show two major ultrastructural changes. 1. The average number of axon terminal profiles present at each endplate decreases. This is thought to reflect the withdrawal of superfluous axons from the endplates. 2. There is an increasing specialization of the postsynaptic structures of the junction: complexity of folding of the muscle junctional membrane increases, as does the accumulation of subjunctional sarcoplasm and muscle nuclei. In soleus muscles treated with alpha BTx, the number of axon terminal profiles observed at the endplates does not decrease, suggesting that elimination of supernumerary axons does not occur. In addition, specialization of the postsynaptic structures of the NMJ is retarded during the period of ACh receptor block.

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“…It is generally believed that the quantal release is responsible for just a tiny proportion (1-4%) of the total amount of ACh that is liberated from mammalian skeletal muscles during incubation under resting conditions (Mitchell & Silver, 1963;Fletcher & Forrester, 1975;Gorio, Hurlbut & Ceccarelli, 1978;Vizi & Vyskocil, 1979;Polak, Sellin & Thesleff, 1981;Miledi, Molenaar & Polak, 1983). This view is mainly based on the disproportion between the large effect of K+-induced depolarization on the frequency of MEPPs and its much smaller effect on the total amount of ACh which appears in the medium, and on other differences between the changes of MEPP frequency and of the total ACh release under various experimental conditions.…”

Section: Introductionmentioning

confidence: 99%

Effects of tetrodotoxin, Ca2+ absence, d‐tubocurarine and vesamicol on spontaneous acetylcholine release from rat muscle.

Doležal

Tuček

1992

The Journal of Physiology

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SUMMARY1. Rat hemidiaphragms were incubated in a physiological low-K+ medium without stimulation and the amount of acetylcholine (ACh) released was measured radioenzymatically. Cholinesterases were inhibited by paraoxon.2. In the presence of 1 ,tM tetrodotoxin (TTX), the amount of ACh released during a 2 h incubation was lowered by 40 %. A similar decrease was observed in the absence of Ca2' and in the presence of 10,tM-d-tubocurarine (dTC). The effects of TTX combined with Ca2+ removal, and of TTX combined with dTC were no greater than those of TTX, dTC or Ca2+ removal alone. TTX and dTC had no effect on the release of ACh from diaphragms 4 days after denervation.3. The reduction of spontaneous ACh release observed in the presence of TTX or dTC or in the absence of Ca2+ is best interpreted on the assumption that about 40 % of the ACh release was due to the impulse activity known to be generated in intramuscular motor nerve branches by the ACh which accumulates after the inhibition of cholinesterases.4. In the presence of 1 and 10 ftM vesamicol (AH5183, 2-(4-phenylpiperidino)-cyclohexanol), the release of ACh was also diminished by approximately 40%. Vesamicol did not augment the inhibition of release produced by TTX or by the omission of Ca2+.5. Since at least 33% of the total ACh release observed was of muscular origin (judging by data from denervated muscles) and about 40% was due to locally generated impulse activity and therefore, most probably, quantal, no more than 27 % of the total ACh release could have represented the sum of random quantal release (giving rise to miniature endplate potentials) and of the non-quantal neural release. Earlier calculations, suggesting that the non-quantal release from motor nerve terminals is responsible for an overwhelming proportion of the total ACh release from neuromuscular preparations incubated under resting conditions in vitro, should be reconsidered by taking into account the likely contribution of nerve impulse activity occurring under 'resting' conditions after the inhibition of cholinesterases.

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Acetylcholine content and release in denervated or botulinum poisoned rat skeletal muscle

Cited by 44 publications

References 23 publications

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice

The effect of postsynaptic block on development of the neuromuscular junction in postnatal rats

Effects of tetrodotoxin, Ca2+ absence, d‐tubocurarine and vesamicol on spontaneous acetylcholine release from rat muscle.

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