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Biomedical subjects

S Thesleff

Publications and source records attributed to S Thesleff.

103 records · Page 6Linked to original sources
PubMed1967

Influence of phospholipase C on some electrical properties of the skeletal muscle membrane.

1. A study was made of the effects of phospholipase C (PhC) on the resting membrane potential, input resistance, action potential and acetylcholine sensitivity of innervated and chronically denervated single muscle fibres of the rat.2. In doses higher than 1.5 mug/ml. PhC significantly increased the ionic permeability of the muscle membrane (indicated by a fall in input resistance) and reduced the resting membrane potential of innervated fibres. The ;fast' or ;white' extensor digitorum longus muscle was the most sensitive and the ;slow' or ;red' soleus the least sensitive muscle. A similar difference was observed among ;fast' and ;slow' muscles of the chicken, the posterior latissimus dorsi being far more sensitive than the ;slow' anterior latissimus dorsi muscle. Chronically denervated muscles were more resistant to these actions of PhC than innervated ones but even after denervation the ;fast' muscles remained more sensitive than the ;slow' muscles.3. The action-potential generating mechanism in the ;fast' and ;slow' muscle was completely and irreversibly blocked by 1.5 mug/ml. of PhC within 1 hr. Furthermore the innervated and chronically denervated muscles were equally sensitive to this effect of PhC. The enzyme caused a gradual increase in the threshold for excitation, reduction in the rate of rise and the amplitude of the action potential. The input resistance and the resting membrane potential were not reduced by this dose of PhC.4. Acetylcholine sensitivity of chronically denervated muscles was not affected by PhC in doses that abolished the electrical excitability of the membrane. When PhC reduced the input resistance and the resting membrane potential a decrease was also observed in the response to applied acetylcholine.5. The results suggest that PhC by acting at the polar heads of membrane phospholipids interferes with the ionic carrier mechanism which generates the action potential. The differences in sensitivity between ;fast' and ;slow' muscles and between innervated and chronically denervated ones are tentatively explained on the basis of heterologous membrane phospholipids and/or variations in their stereochemical arrangement.

Acetylcholine↗
PubMed1966

Nerve implants in botulinum poisoned mammalian muscle.

1. In albino rats the botulinum poisoned gastrocnemius muscle was supplied with an accessory motor nerve in order to investigate whether muscle fibres with structurally intact but non-transmitting synapses would accept additional innervation. As a control similar operations were made in unpoisoned rats.2. One to three months after nerve implantation the muscles were examined histologically for the presence of a new end-plate zone. In botulinum treated muscles 1662 +/- 165 (mean +/- S.D.) of new end-plates were found. In the control animals only a few (90 +/- 13) were observed in the immediate vicinity of the implanted nerve trunk.3. Following recovery from the paralysing action of botulinum toxin electrical stimulation of both the implanted and the original motor nerve evoked strong mechanical twitches in the gastrocnemius muscle.4. When the nerves were stimulated simultaneously little or no summation of tension occurred, indicating that presumably many of the muscle fibres with new end-plates also had functionally intact junctions from the original nerve. The presence of two end-plates in a muscle fibre was confirmed in a few experiments on single curarized fibres by intracellular recording of end-plate potentials on stimulation of each nerve.

Animals↗
PubMedDate not supplied

Increased endocytosis with lysosomal activation in skeletal muscle of dystrophic mouse.

Endocytosis in dystrophic muscles was studied by a combination of biochemical, radiochemical, and light and electron microscopic techniques. It was observed that the uptake of horseradish peroxidase (HRP) and 3H-Inulin in vitro was increased in leg skeletal muscles from dystrophic mice compared with littermate controls. Endocytosis of HRP in vivo was also increased in dystrophic muscles. When HRP was administered intravenously, light microscopic examination of the muscles showed that the macromolecular tracer was present not only in the extracellular space but also as intracellular deposits in several dystropic muscle fibers. Ultrastructural examination of these fibers showed HRP to be present in membrane limited bodies of variable size, some of which likely represented secondary lysosomes, located preferentially close to the A-I junction. HRP was also found inside vacuoles which were sometimes in close vicinity to autophagic vacuoles. Primary uptake vesicles containing HRP appeared to originate from the sarcolemma and the transverse tubules. Biochemical determination of lysosomal enzyme activities revealed elevated levels of both cathepsin D and N-acetylglucosaminidase in dystrophic muscles as compared with controls. The results suggest an increased endocytic activity in dystrophic muscles with distribution of exogenous marcromolecular tracers into endocytic vesicles and lysosomal structures. The hypothesis is put forward that endocytic activity constitutes an important mechanism of lysosomal activation in dystrophic muscles.

Acetylglucosaminidase↗