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| 2. |
- Sellin, L C, et al.
(author)
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Membrane and biochemical alterations after denervation and during reinnervation of mouse skeletal muscle
- 1980
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In: Acta Physiologica Scandinavica. ; 110:2, s. 181-186
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Journal article (peer-reviewed)abstract
- Denervation of the extensor digitorum longus (EDL) muscle of the mouse by either nerve crush or nerve section produced: a reduction of the resting membrane potential (Em), alterations in the properties of muscle fibre action potentials and the development of tetrodotoxin (TTX)-resistant action potentials. These changes in membrane electrical properties were accompanied by an increase in the endocytic activity of the muscle and an increase in the activities of the lysosomal enzymes cathepsin D and N-acetylglucosaminidase (NAGA). Reinnervation of muscle was indicated at 9 days after nerve crush by the presence of miniature end-plate potentials. The recovery of membrane electrical properties, beginning with the onset of reinnervation, were not temporally related. The Em increased in two stages: an early rapid repolarization and a later slower repolarization. The muscle fibers were sensitive to the blocking action of TTX by 12 days after nerve crush, whereas the rate of rise (dV/dt) of the action potential did not approach values of innervated muscles until 21 days. Reinnervation resulted in a decrease in endocytosis and a decrease in the activities of cathepsin D and NAGA toward innervated values by 21 days after nerve crush. The results suggest that membrane alterations after denervation and during reinnervation may occur by endo- and exocytosis of membrane constituents and that the lysosomal system may play a role in the breakdown and/or recycling of these structures.
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| 3. |
- Thesleff, S, et al.
(author)
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Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates
- 1990
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In: British Journal of Pharmacology. - 0007-1188 .- 1476-5381. ; 100:3, s. 487-490
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Journal article (peer-reviewed)abstract
- 1. Tacrine (20 microM) induced, like 4-aminoquinoline (4-AQ, 200 microM), the appearance of a population of miniature endplate potentials (m.e.p.ps) with more than twice the normal amplitude or time-to-peak. The times-to-peak of nerve impulse-evoked endplate potentials were not similarly affected. 2. Cholinesterase inhibition by edrophonium (25 microM) did not prevent tacrine or 4-AQ from inducing this population of m.e.p.ps. 3. Nerve-muscle preparations in which the normal calcium-sensitive quantal release of acetylcholine had been blocked by botulinum neurotoxin type A also responded to tacrine by an increase in the frequency of giant or slow m.e.p.ps. 4. Reduction of the temperature from 30 degrees to 14 degrees C reduced the frequency of giant or slow m.e.p.ps induced either by tacrine or by 4-AQ. A similar effect was obtained by colchicine (5 mM). This supports the idea that proximo-distal axonal transport is required for the secretory activity. 5. The neurosecretion evoked by tacrine could explain the therapeutic effects of the drug claimed in the treatment of Alzheimer's type of dementia.
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| 4. |
- Tågerud, Sven, et al.
(author)
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An ultrastructural study of the segmental uptake of horseradish peroxidase in the endplate region of denervated skeletal muscle fibres
- 1986
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In: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 75:2, s. 141-157
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Journal article (peer-reviewed)abstract
- The segmental uptake of horseradish peroxidase (HRP) in the endplate region of denervated skeletal muscle fibres has been studied ultrastructurally using a method for selecting single muscle fibres with high segmental peroxidase staining from denervated mouse tibialis anterior muscle.Segments containing large peroxidase positive phagosomes could already be seen 10–15 min after i.v. injection of HRP. Such segments were still present 24 h after HRP injection. The localization of phagosomes, deep in the fibres rather than immediately under the sarcolemma, suggests that the uptake occurs from t-tubuli. Vivid proliferation of t-tubuli, consisting of vesiculation, enlargement and encircling of cytoplasmic components, was also observed. The HRP accumulates in phagosomes of varying size and shape. Similar membrane-limited bodies without or with very weak peroxidase staining were also observed. The peroxidase-positive phagosomes participate in autophagic processes as suggested by their content of undegraded cellular material. Golgi profiles, which occurred deep in the muscle fibres, and enlarged components of the sarcoplasmic reticulum were frequently encountered in the segments. Myofibrillar degeneration occurs in the segments and progresses with time after denervation.The described segments may be related to the increased membrane turnover in denervated muscle fibres and/or they may be related to processes aimed at establishing new synaptic contacts.
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| 5. |
- Tågerud, Sven, et al.
(author)
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Effects of botulinum toxin induced muscle paralysis on endocytosis and lysosomal enzyme activities in mouse skeletal muscle
- 1986
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In: Pflügers Archive European Journal of Physiology. - 0031-6768. ; 407:3, s. 275-278
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Journal article (peer-reviewed)abstract
- The effects of botulinum toxin (type A) induced muscle paralysis on endocytosis and lysosomal enzyme activities in skeletal muscle were compared with the effects of surgical denervation. Muscle atrophy, measured as decrease in total muscle protein content, was as large or larger after botulinum toxin treatment as after denervation. Endocytic activity, measured as the in vitro uptake of horseradish peroxidase, and the specific activities of the lysosomal enzymes N-acetyl--d-glucosaminidase and cathepsin D were all increased six days after denervation. Only the specific activity of cathepsin D was increased six days after botulinum toxin poisoning. The uptake of horseradish peroxidase and the specific activity of N-acetyl--d-glucosamidase were also increased eleven days after poisoning. Transverse sections of eleven days botulinum poisoned muscles from animals injected with horseradish peroxidase showed fibres with dense peroxidase staining similar to those seen in denervated muscle although they seemed to occur less frequently.The results show that increases in endocytic activity and lysosomal enzyme activities may occur in skeletal muscle without the presence of degenerating axons. The differences in effects of surgical denervation and botulinum toxin induced paralysis are discussed in terms of what is known about the mechanism of action of botulinum toxin and the possible functional roles of the two lysosomal enzymes studied.
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