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Biomedical subjects

G Goldspink

Publications and source records attributed to G Goldspink.

At least 91 records · Page 5Linked to original sources

The importance of stretch and contractile activity in the prevention of connective tissue accumulation in muscle.

The loss of serial sarcomeres which results when muscles are immobilised in a shortened position is accompanied by an increase in the proportion of collagen and an increased muscle stiffness. In order to determine whether it is lack of stretch or lack of contractile activity which is the main factor involved in these changes experiments were carried out using different combinations of immobilisation and electrical stimulation. It was found that the connective tissue accumulation that occurs in inactive muscles can be prevented either by passive stretch or by active stimulation. It was also shown that in muscle that is working over a reduced range there is, as in muscle immobilised in the shortened position, a reduction in serial sarcomeres. In this case, however, there is no concomitant increase in connective tissue, again indicating that contractile activity is important for the maintenance of normal muscle compliance.

Animals↗

Changes in fibre type, number and diameter in developing and ageing skeletal muscle.

Morphometrical and histochemical features of muscle undergo continuous changes with age. Two representative muscles were studied to determine the nature of these changes, the extensor digitorum longus and the soleus. Muscle fibre type ratios were found to change with age so that there were more oxidative types. In the extensor digitorum longus the cross sectional area occupied by fast oxidative glycolytic fibres increased, while in the soleus fast oxidative glycolytic fibres apparently underwent conversion into slow oxidative fibres. Muscle fibre diameter increased dramatically during early growth but later in senile animals there was evidence of both atrophy and splitting. In the extensor digitorum longus the uneven growth of the two dominant fibre types gave rise to a bimodal fibre diameter distribution. The soleus, which is composed of predominantly one fibre type, did not show bimodality. Senile muscles had a characteristic wide distribution of fibre diameters with ill defined peaks. Total fibre number in the extensor digitorum longus decreased in early life while total fibre number in the soleus remained unchanged.

Aging↗

Effects of hypokinesia and hypodynamia upon protein turnover in hindlimb muscles of the rat.

Hypokinesia/hypodynamia was induced in the hindlimb muscles of the rat using a suspension technique. This caused differing degrees of atrophy in different muscles, however, this atrophy was reduced in muscles held in a lengthened position. The greatest degree of wasting was observed in the unstretched soleus, a slow postural muscle, where both Type 1 and Type 2a fibers atrophied to the same degree. However, wasting of the gastrocnemius muscle was associated with a reduction in the size of the Type 2b fibers. In both slow postural and fast phasic hindlimb muscles, atrophy was brought about by a reduction in the rate of protein synthesis in conjunction with an elevation in the rate of protein degradation. When inactive muscles were passively stretched, both protein synthesis and degradation were dramatically elevated. Even periods of stretch of as little as 0.5 h.d-1 were found to significantly decrease atrophy in inactive muscles.

Animals↗

The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat.

An animal suspension model has been used to simulate the weightlessness experienced during space travel. This procedure results in a reduction in the normal shortening (i.e. hypokinesia) and force generation functions of hind limb muscles (i.e. hypodynamia). The ensuing muscle atrophy was studied over 12 days in different muscle types. Slow muscles (e.g. the soleus) underwent a more pronounced atrophy than intermediate (i.e. gastrocnemius) and fast phasic muscles (e.g. extensor digitorum longus). In all muscle types inactivity resulted in a smaller accumulation of DNA and losses of RNA and protein after 5 days. The latter arose from a decrease in the rate of protein synthesis (measured in vivo) and an increase in protein breakdown. Increased specific activities of cathepsins B and D also supported the view that there is an increased proteolysis after hypokinesia and hypodynamia. When the inactive soleus was simultaneously held in a lengthened (stretched) state the atrophy was prevented through a large increase in the fractional rate of protein synthesis. Protein degradation remained elevated with stretch, thereby slowing the growth of these muscles relative to those in pair-fed, ambulatory controls. The much smaller atrophy of the tibialis anterior and extensor digitorum longus muscles in suspended only limbs represented an underestimate of the true atrophic effects of hypokinesia and hypodynamia. In this model gravity pulls the suspended foot into a plantar flexed position, thereby permanently stretching and protecting such flexor muscles. When this influence of stretch was removed a greater atrophy ensued, mainly due to the loss of the stretch-induced stimulation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of stretch combined with electrical stimulation on the type of sarcomeres produced at the ends of muscle fibers.

Stretching a muscle results in a rapid addition of sarcomeres at the ends of the muscle fibers. The effect of a pattern of electrical stimulation resembling that of a slow motoneuron on the newly formed muscle tissue in a stretched, fast-contracting muscle was investigated. We found that after a period as short as 4 days, the type of sarcomeres which were added on to the ends of the existing myofibrils differed from those in the middle regions of the experimental muscles: there was a much higher proportion of type I and type IIA sarcomeres in the stretch-stimulated ends. This study showed that reprogramming of the synthesis of fiber type-specific contractile proteins can be achieved and detected within a very short time by using electrical stimulation combined with stretch.

Animals↗

Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles.

A state of hypokinesia and hypodynamia has been induced in the hindlimb muscles of the rat (100 g) using a suspension model. The ensuing muscle atrophy was assessed by reference to muscles in fully mobile control animals, which were either fed ad libitum or fed the same lower food intake of the suspended animals. Over a total of 7 days of suspension the slow-twitch postural soleus muscle underwent a much greater atrophy than the fast-twitch phasic extensor digitorum longus. Changes with respect to the position of the suspended foot, and hence muscle length, necessitate caution in comparing the extent of the atrophy between different muscle types. After 3 days of inactivity the atrophy of the soleus muscle was explained by a 21% decrease in the fractional rate of synthesis (measured in vivo) and a 100% increase in the rate of protein breakdown. The reduction in the synthetic rate was associated with a net loss (23%) of RNA and hence muscle ribosomes. In contrast when this inactive soleus muscle was permanently stretched the RNA content (44%) and protein synthetic rate increased (59%) markedly above control values. Although protein breakdown remained elevated in this stretched muscle, the extent of the atrophy in response to hypokinesia and hypodynamia was greatly reduced.

Animals↗

Myofibrillar ATPase activity in the carp Cyprinus carpio: interactions between starvation and environmental temperature.

The myofibrillar ATPase activity of the epaxial white muscle was measured in carp Cyprinus carpio L. acclimated to 10 degrees C or 28 degrees C. As previously reported, cold acclimation was associated with an increase in the ATPase specific activity and a decrease in the thermostability. The water content of the white muscle was significantly higher in cold-acclimated fish than in warm-acclimated fish (P less than 0.002). Starvation for 10 weeks resulted in a significant increase in the white muscle water content of both warm- and cold-acclimated fish (P less than 0.002). When carp were starved, the ability of the myofibrillar ATPase to show thermal compensation disappeared. Previously acclimated fish, when starved, showed steady alterations of the myofibrillar ATPase activity to a level mid-way between the acclimated extremes. Refeeding resulted in a gradual return to the normal acclimated level.

Acclimatization↗

Malleability of the motor system: a comparative approach.

The various ways in which the power output of muscles can be changed are described. As a result of exercise and growth, force production is increased by an increase in the cross-sectional area of the fibres. This is associated with changes in the rate of synthesis and degradation of muscle proteins which lead to build up of the myofibrils. These then split longitudinally when they reach a critical size. This process is repeated so that the number of myofibrils increases very considerably. Also, during growth, the displacement is increased by increasing the length of the muscles. To do this more sarcomeres are produced in series along the length of the fibres. This is induced by stretch which also encourages fibre growth in girth as well as in length. Yet another way of changing the power output of a muscle is to change the types of muscle fibres (motor units) within the muscle. Fibre type transformation has been fibres (motor units) within the muscle. Fibre type transformation has been shown to occur with cross innervation and stimulation but it does not usually occur with exercise training. It has been possible, however, to change the fibre type proportions in young animals. Also, by combining stretch with stimulation, it has been possible for instance to make the fast glycolytic fibres add on fast oxidative type sarcomeres or even slow oxidation type sarcomeres. Interestingly, fibre transformation also occurs in some species of fish during acclimation to low temperatures in that the specific myofibrillar ATPase activity is increased. This means that the reduction in power output due to decreased temperature is to some extent compensated for by an increase in the intrinsic rate of shortening. EMG studies of fish swimming at different temperatures have shown that the acclimated fish can swim faster and can derive more aerobic sustainable power as a result of this change.

Adaptation, Physiological↗

The effect of reduced activity on the enzymatic development of phasic and tonic muscles in the chicken.

The effects of reduced activity (immobilisation) on the development of the contractile enzyme, Mg2+-activated myofibrillar ATPase was studied in a tonic muscle, the anterior latissimus dorsi and in a phasic muscle, the posterior latissimus dorsi of the chicken. Mg2+-activated myofibrillar ATPase activity showed a decreased and delayed activity peak in both the immobilised muscles. Large differences between the two muscles were observed using this marker enzyme. These data indicate that the activity of Mg2+-activated myofibrillar ATPase and the associated differential gene expression involved in fibre type differentiation are influenced by the early activity pattern of the muscles.

Adenosine Triphosphatases↗

Changes in fiber type composition in growing muscle as a result of dynamic exercise and static overload.

The effects of dynamic exercise (jumping) and static overload (synergist tenotomy) on rat soleus muscle were investigated during a growing phase in juvenile animals. The relative proportions of slow twitch (type 1), fast twitch (type 2a) and intermediate (type 2c) fibers were determined histochemically. The control animals, as part developmental process, lost type 2a fibers apparently by conversion to type 1 fibers via the type 2c form. Synergist tenotomy enhanced the conversion of type 2a fibers to type 2c fibers as these muscles displayed fewer type 2a fibers than control animals at the same age. In contrast, the dynamic exercise delayed the loss of type 2a fibers from the soleus. When the two exercises were combined the effects on fiber type proportions cancelled each other; this group also had a large number of type 2c fibers. This present study indicates that the activity imposed on a muscle influences the maturational development of the constituent fiber types.

Animals↗

Muscle development in thyroidectomised chickens (Gallus domesticus).

The metabolic and contractile activity of muscle was determined in immature cockerels made hypothyroid by surgical thyroidectomy at 6 weeks of age. Four weeks after thyroidectomy the activity of Mg2+-activated myofibrillar ATPase and total phosphorylase was reduced in the fast-phasic, posterior latissimus dorsi (PLD) and scapulotriceps (ST) muscles. The activities of these enzymes were unaffected in the slow-tonic, anterior latissimus dorsi (ALD) muscle. Thyroidectomy had no effect on length of the muscles studied but reduced the weight of the ALD and ST muscles. These results suggest that hypothyroidism results in a "slowing down" of fast-phasic muscles, although it does not affect the activity of slow-tonic muscles.

Adenosine Triphosphatases↗

Possible use of an indicator muscle in future breeding experiments in domestic fowl.

Domestic fowl were chosen for different body weights in descending order of size, viz. Tetra, Rhode Island Red/Light Sussex cross, White Leghorn and Bantam. The numbers and sizes of fibres in various muscles were determined by quantitative histology, and fibre number was also estimated by DNA measurement. In contrast to the situation in mammals, fibre size (diameter) was of greater importance than fibre number in determining muscle size. Biochemical measurement of DNA content in a muscle was not a reliable estimate of cell number without histological verification. It is suggested that the anterior latissimus dorsi muscle could be used as an indicator muscle in future selective breeding programmes for fibre number because of its fibre arrangement and accessibility.

Animals↗

Muscle fiber activity in carp as a function of swimming speed and muscle temperature.

These experiments were performed to determine how ectothermal animals maintain their locomotory ability during acute changes in muscle temperature, despite the large thermal dependence of the mechanical properties of their muscle. The electrical activity of the red (slow-twitch) and white (fast-twitch) muscle fibers of carp was monitored while the carp swam at various speeds at 10 and 20 degrees C. The patterns of recruitment of different fiber types were similar at both temperatures. At low speeds only the red muscle was active, whereas at high speeds the white muscle was active as well. The swimming velocity at which white muscle was initially recruited increased from 26 cm/s at 10 degrees C to 46 cm/s at 20 degrees C. These results suggest that the order of recruitment of motor units was the same at 10 and 20 degrees C but that the recruitment occurred over a narrower range of speeds at the low temperature. Hence, to generate the muscle power required to swim at a certain velocity, fish recruit more muscle fibers, which include faster fiber types when their muscle is cold than when their muscle is warm.

Animals↗

Connective tissue changes and physical properties of developing and ageing skeletal muscle.

Selective staining of the connective tissue and image analysis showed that in the extensor digitorum longus and soleus muscles of the rat there was an increase in the thickness of the endomysium in both early growth and senility. The perimysium thickness was more or less constant throughout life except in senility when the concentration of this component also increased. The stiffness (length-passive tension) of these muscles was found to increase throughout life. Log transforms of the length-passive tension plots had particularly steep slopes in the senile extensor digitorum longus muscle. Except in the senile soleus muscle, the increase in stiffness was closely correlated with the increase in endomysium and perimysium and with total muscle collagen (as measured biochemically) with age. The relationship between the initial length and the active tension in the extensor digitorum longus muscle changed with age. The older muscles showed a greater decline in tension for each decrement of length resulting from the increased development of the connective tissue.

Aging↗

Connective tissue changes in immobilised muscle.

The reduction in fibre length of muscles immobilised in a shortened position is accompanied by reduced compliance of the muscle. Since the intramuscular connective tissue framework distributes the forces passively imposed on a muscle by stretching, it was decided to investigate the amount and distribution of connective tissue in immobilised muscles. Biochemical analysis of the hydroxyproline content of muscles immobilised in the shortened position for different periods of time showed an increase in the ratio of collagen to muscle fibre tissue. This occurred during the first few days of immobilisation, before there was any significant loss of sarcomeres. Thus the increase in connective tissue appeared to result directly from immobilisation rather than from redistribution of connective tissue, following shortening of the fibres. A detailed histological analysis of muscle sections stained for connective tissue with Sirius Red showed that the early increase in connective tissue in immobilised muscles occurred in the perimysium rather than the endomysium, although after a longer period of immobilisation there was also a thickening of the endomysium. Ultrastructural analysis of the perimysium in normal muscle showed that the angle the collagen fibres made with the muscle fibres changed with the state of stretch of the muscle; when the muscle was shortened, the angle was larger than when the muscle was lengthened. In immobilised muscle, collagen fibres were found to be arranged at a more acute angle to the axis of the muscle fibres than was found in normal muscle; this would be expected to affect the compliance of the muscle. The experiments described indicate that the increased stiffness of immobilised muscles could result from both quantitative and qualitative changes in the connective tissue.

Animals↗

Differentiation of muscle and the determination of ultimate tissue size.

The factors that determine ultimate muscle size have been studied using a "model" that involves two strains of mice, which had been especially bred for "largeness" (QL) and for "smallness" (QS). The difference in muscle size was not found to be due to a difference in fibre size, but due to a difference in fibre number. The muscles from the "QL" mice contained about 30% more fibres. The reason for this increased fibre number was investigated. During early development, the fusion of mononucleated presumptive myoblasts to form multinucleated myotubes took place at the same time in both "QL" and "OS" mice, as indicated by the appearance and increase in activity of ATP: creatine phosphotransferase. At this stage fibre (and cell) number and size could be determined by measuring nuclear number and protein/DNA ratio respectively. No difference in fibre (and cell) size could be found in mice at 5 days before birth, newly born, or at 20 days of age. At these ages it was found that the muscles from the "QL" mice contained a greater number of nuclei (muscle cells). The amount of RNA/nucleus was used as an index of protein synthetic rate, and no difference could be found between the large mice and the small mice. It was concluded that, in the case of the "QL" mice, the increased fibre number was not brought about by: (i) a delay in time of fusion of presumptive myoblasts; (ii) a smaller number of myoblasts fusing to form myotubes; or (iii) extensive fibre formation after fusion. Differences in fibre number, and hence muscle size, must therefore, presumably be caused by initial differences in the rate of proliferation of myoblasts before fusion.

Animals↗

Energetics of isometric contraction in dystrophic fast and slow muscles.

The amount of phosphoryl creatine (PC) hydrolysed during a ten-second isometric contraction was measured in the biceps brachii (fast) and soleus (slow) muscles of adult normal and dystrophic mice (Re 129 strain) following inhibition of glycolysis and oxidative phosphorylation. The dystrophic muscles were found to have a lower isometric economy (tension-time integral per mumol PC) than the normal muscles. This was particularly so in the case of the fast biceps brachii muscle which is affected by dystrophy to a greater extent than the slow soleus muscle. The isometric economy of the dystrophic muscles was lower even when the results were based on a total creatine rather than on a weight basis. This suggests there may be some defect in the contractile proteins of dystrophic muscle. The normal soleus muscle was found to be approximately three times more economical in maintaining tension than the normal biceps brachii muscle. This indicates the adaptation of slow muscles such as the soleus are used for maintenance of posture.

Animals↗