Fast Extensor Digitorum Longus Muscles Research Articles

Effect of denervation on glucose uptake in rat soleus and extensor digitorum longus muscles.

From 1 to 14 days after denervation, glucose uptake in the fast extensor digitorum longus and slow soleus muscles in rats was investigated and compared with that of the corresponding intact contralateral muscles. Denervation-induced atrophy in soleus was greater than that in extensor digitorum longus muscle. Glucose uptake in extensor digitorum longus muscle increased significantly, but that in soleus decreased significantly.

雌雄ラット骨格筋における代謝特性の加齢変化

The present study has been undertaken aiming at the elucidation of the effect of growth and sex-related difference on metabolic properties of skeletal muscle in rat hindlimb. The slow soleus (SOL)and the fast extensor digitorum longus (EDL) muscles were obtained from Wistar strain rats aged from 3 to 75 weeks after birth. The results are summarized as follows: 1. The male rats, after 6 weeks of age, showed significantly higher increase in the body weight than the female. 2. The muscle weight gradually increased until 25 or 30 weeks of age in both sexes. The muscle weights of the SOL and EDL in female were always smaller than those in male at any period of age. 3. The glycolytic enzyme activity, obtained biochemically, in the EDL rised slowly with growth, but not in the SOL. The mean activity of oxidative enzyme in the SOL dropped with growth. There was a significant difference in oxidative enzyme activity between SOL and EDL of younger rat (up to 12 weeks of age). Beyound 12 or 15 weeks of age, however, the oxidative enzyme activity in the SOL dropped to the level of that obtained in EDL. 4. In the rats younger than l0 to 20 weeks, the glycolytic and oxidative enzyme activities of both muscles were greater in female rats than in ma1e. This inclination was reversed after the age of 20 weeks. It is concluded that the properties of glycolytic and oxidative enzyme activities in rat skeletal muscle are influenced by growth. A sex-related variation in the enzyme activity exists especially in the EDL muscle.

Stimulation of denervated rat soleus muscle with fast and slow activity patterns induces different expression of acetylcholinesterase molecular forms

The relative amount and distribution of acetylcholinesterase (AChE) molecular forms were studied in slow soleus and (less extensively) in fast extensor digitorum longus (EDL) muscles of the rat before and after denervation and direct stimulation. Normal EDL muscles showed higher total and specific AChE activity than normal soleus muscles and contained essentially three different molecular AChE forms (G1, G4, and A12) as opposed to six forms (G1, G2, G4, A4, A8, and A12) in the soleus. Denervation reduced AChE activity in both muscles. In the soleus direct stimulation starting 2 to 3 weeks after denervation increased the specific AChE activity markedly. The increase started 12 to 24 hr after the onset of stimulation, reached 3 to 5 times normal values after 2 to 7 days, and then declined gradually toward normal values over the next 2 weeks. Furthermore, the effect on the different molecular forms depended strongly on the stimulus pattern. Thus, intermittent 100 Hz stimulation (fast pattern) induced essentially the three forms typical of the normal EDL, whereas continuous 10 Hz stimulation induced the six forms characteristic of normal soleus muscles but with some differences in their relative proportions. In the EDL, 2 days of continuous 10 Hz stimulation (the only duration and pattern examined) failed to induce a similar increase in AChE activity.

Colchicine-induced differential sprouting of the endplates on fast and slow muscle fibers in rat extensor digitorum longus, soleus and tibialis anterior muscles

The patterns of sprouting of motor endplates were examined in fast extensor digitorum longus and slow soleus muscles and in tibialis anterior muscles containing fast and slow muscle fiber types. A histochemical technique combining nerve silver impregnation and endplate cholinesterase staining was developed for this task. Temporal examination of the innervation was conducted 3,7 and 10 days after either a 45 or 90 min application of the ipsilateral sciatic nerve with 5 mM colchicine. This dosage of drug did not cause detectable axon or muscle fiber degeneration, unlike 60 mM which was highly neurotoxic. At 3 days following treatment with the lower concentration, there were no significant differences in the percentages of intranodal, preterminal and ultraterminal sprouts between the normal (non-treated), sham-treated, contralateral systemic-control and drug-treated groups of muscles. By 7 and 10 days, the muscles on the drug-treated side exhibited significant increases in the 3 types of sprouts. Collateral sprouting was uncommon: most outgrowths remained on the muscle fibers innervated by the parent axons. Endplates in the tibialis anterior muscles of the control and drug-treated groups were classified Complex, Intermediate or Simple according to the relative degrees of branching of the terminal arbors. The occurrence of endplate classes and muscle fiber types was correlated in the superficial and deep regions of this muscle. Complex endplates innervated fast glycolytic fibers, Intermediate endplates supplied fast oxidative glycolytic fibers, and Simple endplates served slow oxidative fibers. In response to colchicine, the endplates of the slow muscles sprouted more than those of fast muscles while the innervation of slow fiber types sprouted less than that of fast fiber types. Furthermore, intranodal sprouts were more prevalent in slow muscles and ultraterminal sprouts more numerous in fast muscles whereas intranodal sprouts predominated on fast fiber types and ultraterminal sprouts were characteristics of slow fiber types. These apparently contradictory results were reconciled when it was noted that soleus endplates were mostly Complex and Intermediate, and the extensor digitorum longus contained more Simple endplates. Thus, consistency of sprouting patterns among endplate types of the 3 muscles was recognized when the pre-existing branching patterns were considered. This indicated that the patterns of sprouting were determined by the motor neurons rather than the muscle fibers. The observed sprouting responses supported the hypothesis that colchicine treatment of motor axons caused muscle fibers to elaborate a diffusible sprout-inducing factor.

Soluble phosphatidylinositol phosphodiesterase in normal and denervated fast and slow muscles of the rat.

Phosphatidylinositol phosphodiesterase activity was determined in cytosol prepared from rat slow (soleus) and fast (extensor digitorum longus) muscles. The substrate was prepared by incubation of sarcoplasmic reticulum with myo-[2-3H]inositol. The enzyme hydrolysed both membrane-bound and extracted phosphatidylinositol. The activity determined with the isolated phospholipid exhibited an optimum at pH 5.5. Ca2+ ions stimulated the activity. The enzyme specific activity was higher in cytosol prepared from soleus muscle than in that from extensor digitorum longus muscle. After section of the motor nerve, the activity of the enzyme increased in both muscles up to 36 h and then declined. A function for this enzyme in the control of acetylcholine sensitivity in muscle is discussed.

Contractile and fatigue properties of thyrotoxic rat skeletal muscle.

The effects of thyrotoxicosis on the contractile properties and development of muscle fatigue in the slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles were examined in rats given 3 mg of L-thyroxine and 1 mg of L-triiodothyronine per kilogram of diet for 6 weeks. The hormone treatment produced significant decreases in the contraction time, one-half relaxation time, and twitch tension in the SOL, while the peak rate of tension development (+ dP/dt) and decline (- dP/dt) in this muscle were elevated. Additionally, the force-frequency curve was shifted to the right and, thus, resembled the curve of a normal fast-twitch muscle. In contrast, the contractile properties of the fast EDL were relatively unaltered by the hormone administration. Thyrotoxicosis also changed the SOL response to contractile activity as twitch tension, + dP/dt, and - dP/dt remained high, and a faster decline in muscle glycogen and an increase in lactate occurred compared to control muscles. These results clearly demonstrate a preferential effect of thyroid hormone on slow compared to fast skeletal muscle.

Differential effect of nerve injury at birth on the activity pattern of reinnervated slow and fast muscles of the rat.

The activity patterns of the reinnervated slow soleus and fast extensor digitorum longus (e.d.l.) muscles were studied in rats during the first 6 months after sciatic nerve crush at birth, using chronic electromyography. When the nerve lesion was inflicted shortly after birth, the recovery of the muscle weight and size was always much less than if the same lesion was inflicted on adult animals. As previously demonstrated, this effect is due to motoneurone and muscle fibre loss. Following reinnervation after a neonatal crush, the soleus muscle recovered its normal tonic activity pattern during postural and spontaneous locomotor activity. By contrast, in the reinnervated e.d.l. muscle, abnormal tonic motor unit activity was recorded during locomotion, in addition to the phasic activity characteristic of the normal muscle. In response to postural reflexes elicited by tilting the animal, tonic motor unit activity was recorded from the reinnervated e.d.l. muscle, whereas the normal muscle was not activated by these stimuli. The aggregate activity recorded from the reinnervated e.d.l. during spontaneous locomotion was about 2-3 times greater than normal, whereas in the reinnervated soleus no significant change took place. In animals which had their nerves crushed as adults, the activity pattern and aggregate activity of both muscles was similar to normal. The firing pattern of individual motor units from normal and reinnervated muscles was compared. After a neonatal crush, the mean frequency of firing of e.d.l. motor units was significantly lower compared to normal or to that after an adult crush, whereas in soleus no significant change was found. These results indicate that peripheral nerve lesions during early development affect predominantly the development of motoneurones with a phasic, high-frequency discharge pattern resulting in a shift towards tonic, lower-frequency motor unit activity.

Temperature sensitivity of tension development in a fast-twitch muscle of the rat.

Isometric contractions of the biceps brachii (short head) muscle in the rat were recorded in vitro with direct stimulation and at different temperatures (range, 35 degrees C-10 degrees C). In confirmation of our previous findings from fast extensor digitorum longus and slow soleus muscles, the time and rate parameters of the twitch and the tetanus showed an increased temperature sensitivity below 20 degrees C. The dependence on the initial muscle length of the rate of rise of tetanic tension was examined at 27 degrees C and at 15 degrees C. When represented as a percentage of the tetanic tension at each length, the rate of rise was independent of muscle length at both temperatures. Our interpretation of this particular observation is that the increased cooling depression of the rate of tension rise below 20 degrees C is not associated with a qualitative change in its underlying basis.

Changes of activity patterns in slow and fast muscles during postnatal development

The motor activity patterns of the slow soleus and the fast extensor digitorum longus (EDL) muscles of the rat were studied by electromyography (EMG) in the awake unrestrained animal during postnatal development. In the adult soleus, tonic, low frequency activity of motor units was recorded at rest and during movement. In animals less than 12 days old the muscle was activated phasically, the motor unit firing frequency was slightly lower than in the adult, and tonic discharges were absent at rest. After this time, tonic postural activity gradually developed and resembled the adult pattern by 3 weeks of age. The adult EDL muscle was silent at rest and was activated phasically at high frequencies during movement. In animals of less than 12 days of age the muscle was also activated phasically but at lower frequencies. The firing frequency increased to adult values during the second and third week of postnatal development. The discharge properties of motor units from soleus and EDL were compared in rats of different ages. There was a greater variability of interspike intervals during firing in motor units from very young animals than in adults. Whereas in adult animals it was possible to discern a graded recruitment of motor units, animals less than 10 days old showed no regular recruitment order and some motor units appeared to be activated synchronously.

A distinct difference between slow and fast muscle in acetylcholinesterase recovery after reinnervation in the rat

The changes in acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activity in nerve proximal and distal to the crush site as well as in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle were studied during denervation and reinnervation in rat. Within 24 h after nerve crush, conduction in the distal nerve and neuromuscular transmission was lost. In the distal nerve segment, AChE and CAT activity showed no initial increase and was reduced to 25% 14 days after crush. During the reinnervation period, AChE and CAT activity recovered to 50% (AChE) and 80% (CAT) of control values and CAT activity in the EDL and SOL muscles followed closely the changes in distal nerve. In muscle, AChE activity was reduced to 15% by 2 weeks postoperatively. Enzyme activity in EDL recovered to 50% of control activity in 5 weeks after crush. In the SOL, end-plate and non-end-plate regions' AChE activity recovered at a faster rate, resulting in a temporary increase in AChE activity to more than control values during the third and fourth week. By the end of the fifth week, AChE activity had returned to control activity. Turnover values for AChE based on the reinnervation data showed a half-life value for AChE in proximal nerve of 32 days, in distal nerve 42 days, in EDL 23 days, and for SOL 5.1 days. The half-life for AChE in both muscles was significantly shorter than that of the nerve, indicating that the nerve did not supply AChE to the muscles. Half-lives for CAT calculated on the basis of the reinnervation data were 11.6 days for proximal nerve, 18.4 days for distal nerve, and 30 days for SOL and EDL muscles. It is concluded that the ability to synthesize AChE in end-plate and non-end-plate regions of muscle is an endogenously programmed event in the development of both fast and slow muscles. The nerve initiates and maintains the synthesis and can modify the rate of synthesis in individual muscle fibers. The mechanism by which the nerve stimulates and maintains AChE synthesis in muscle may be related to the release of trophic factors muscle activity or to a combination of these and other factors still to be investigated.

The action of dantrolene sodium on rat fast and slow muscle in vivo.

1. Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a carrier solution of 5% mannitol taken to pH 10 with NaOH. This carrier solution itself was without effect on extrafusal muscle contraction. 2. Dantrolene sodium (5 mg/kg) had a greater depressant action on the twitch contraction of the fast extensor digitorum longus (EDL) muscle than on the slow soleus (SOL) muscle. The EDL twitch was depressed to 25.9% +/- 1.2% (mean + s.e. mean, n = 7) of control whereas the SOL twitch was depressed to 31.3% +/- 0.4% (n = 9). These values were significantly different at the P less than 0.001 level. 3. The twitch contraction time to peak was reduced by approximately 35% in both EDL and SOL by dantrolene sodium. However, the drug reduced the half relaxation time of SOL by approximately 30% but that of EDL was hardly affected. 4. The effect of dantrolene sodium on contractions elicited by repetitive stimulation was dependent upon the stimulation frequency. For the SOL muscle the greater depression was produced at a stimulation frequency of 25 Hz and for EDL at 75 Hz. The minimum of depression was produced for a full fused tetanus for both muscles. 5. The significance of these findings is discussed in terms of the action of dantrolene sodium on motor control in the intact animal.

Comparison of contractile, histo- and biochemical properties of different skeletal muscles of the brown rat (Rattus norvegicus) with those of the domesticated Wistar rat

1. Muscle properties of rat strains showing different locomotor activities were studied. The isometric contraction times (CT) of the slow soleus muscle are shorter in both young and adult domesticated Wistar than in wild brown rats; no difference was found in the fast extensor digitorum longus (EDL) muscles. No significant difference was seen with respect to half relaxation time (HRT) in either fast or slow muscles. CT and HRT of the diaphragm are longer in young brown rats than in domesticated animals, while the diaphragm of the adult wild rat differs only by a longer HRT. 2. Histochemically, the fast EDL muscle and diaphragm show different types of muscle fibres, i.e. fibres with low and high myofibrillar ATPase activity (type I and II), and fibres with low, intermediate and high succinic dehydrogenase (SDH) activity (type A, B and C). The EDL and diaphragm of brown rats have a higher percentage of “fast-red” fibres with high ATPase and SDH activities (type II C) and phospholipid content, than the Wistar rats. The slow soleus muscles of young and adult brown rats are uniform with respect to low ATPase activity and heterogeneous with respect to SDH activity; in the Wistar rat the soleus muscles are heterogeneous with respect to both myosin ATPase and SDH activities, i.e. they contain “slow-intermediate” (I B) and “fast-red” (II C) fibres. The pattern of phospholipid content is similar to the SDH pattern in each case. No difference was found in phosphorylase activity. The glycogen content is higher in both fast and slow muscles of the adult rat than in the muscles of the domesticated rat.

Transposition of the soleus into the bed of the extensor digitorum longus muscle in the rat

In 38 rats the slow soleus muscle was transposed, with its neurovascular bundle intact, into the bed of the fast extensor digitorum longus muscle. Transposed muscles underwent degeneration and regeneration like free muscle grafts. Both contractile and histochemical properties remained those of the soleus muscle, supporting the conclusion that the nerve to a slow muscle is pre-eminent in determining the functional and histochemical characteristics of the muscle.

Appearance in slow muscle sarcolemma of specializations characteristic of fast muscle after reinnervation by a fast muscle nerve

We utilized quantitative freeze-fracture electron microscopy to study the plasticity of orthogonal clusters of 60-Å particles (the “square array”) found in the sarcolemma of fast-twitch muscle. The membrane macromolecular composition of normally slow-twitch rat soleus muscle was examined 1 year after surgical reinnervation by the nerve from fast-twitch extensor digitorum longus muscles. The isometric contraction times and histochemical profiles were monitored and it was confirmed that conversion of fiber types had occurred. The sarcolemma of the switched “fast” soleus developed square arrays of 60-Å particles characteristic of fast-twitch muscle whereas the sarcolemma of the contralateral control, the “slow” soleus, contained only random particles. Square array density per square micrometer in cross-reinnervated fast soleus fibers resembled that of normal fast extensor digitorum longus muscles and varied as a function of distance from the neuromuscular junction. This experiment demonstrates that the appearance of these unusual clusters of 60-Å particles is neuronally regulated. We further suggest that these macromolecules are under the influence of the same subtle aspects of innervation that regulate the differentiation of myosin adenosine triphosphatase and thereby the contractile behaviors of fast- and slow-twitch muscle. The function of the sarcolemmal square array is unknown; however, a correlation with a membrane property that is more highly developed in fast-twitch muscle is to be expected.

Differentiation of myosin in soleus and extensor digitorum longus muscle in differnt animal species during development.

CA2+-ATPase activity and light chains of myosin prepared from fast and slow muscles of rat guinea-pig and rabbit were studied during development from embryonic to old age to establish further correlation with the well-known developmental changes in contraction properties of these muscles. The changes involve the slow soleus muscle much more than the fast extensor digitorum longus muscle. Myosin-ATPase activity of the soleus muscle before or at birth is higher than in the muscle of adult animals. Myosin from the soleus muscle of embryos or newborn animals reveals light chains of myosin of both fast and slow type (with a preponderance of light chains of fast type in 26-days-old rabbit embryos). During postnatal development the amount of light chains of the fast type decreases, that of the slow type increases. Myosin from the soleus muscle of adult animals contains only light chains of the slow type. However, myosin from the soleus muscle of 30-months-old rats exhibits high myosin ATPase activity and contains light chains of myosin of both slow and fast type as in perinatal development. This is in agreement with the shortening of contraction time observed in this muscle in very old age. Thus developmental differentiation of myosine in the soleus muscle is followed by a trend of levelling out of the differences between fast and slow muscles of senescent animals. No such "biphasic" development is observed with respect to the fast extensor digitorum longus muscle.

A freeze-fracture study of sarcoplasmic reticulum from fast and slow muscle of the mouse.

Sarcoplasmic reticulum (SR) of fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of the mouse was examined by freeze-fracture techniques. A distinctive feature of sarcoplasmic reticulum from the EDL is the presence of hillocks on the A-face within the terminal cisterns. These hillocks are usually arranged in a single row which is deployed parallel to the long axis of the adjacent T-tubule. Center-to-center spacing of hillocks within a row is about 70-75 nm. Hillocks are also found scattered within the collar region. The EDL of ten week mice was characterized by sheet-like terminal and intermediate cisterns, the latter being replaced in 37 week animals by thin tubular longitudinal elements of the SR which contain no hillocks or dimples. Hillocks occur only occasionally in SR from 10 or 20 week SOL muscle. In such cases the hillocks occur singly rather than in rows as in the terminal cisterns of EDL. The predominant form of SR in the SOL contains no hillocks. Total particles in the A-face of EDL-SR (2996 particles/mu2; S.D. = +/- 287) slightly exceeded that of SOL-SR (2558 particles/mu2; S.D. = 274 8 NM). Packing density of 8 nm particles was slightly higher for EDL (750/mu2) VS. SOL (700/mu2). The possible significance of these features of SR in fast and slow muscle is discussed.

Effect of vinblastine on neural regulation of metabolism in rat skeletal muscle

Chronic application of vinblastine, a substance known to disrupt axoplasmic flow, to nerves innervating the fast extensor digitorum longus and slow soleus muscles of the rat, produces electrophysiological signs of denervation (depolarization and extrajunctional acetylcholine sensitivity), but does not alter motor activity. We therefore examined the effects of vinblastine treatment on those metabolites and enzymes that are known to change after denervation of fast and slow skeletal muscle. A silastic cuff containing 0.1% vinblastine was placed around sciatic nerves of adult rats for 5 days. Glucose-6-P decreased 68% in the extensor, but did not change in soleus muscles. Phosphocreatine also decreased slightly, but significantly, in the extensor. Thus, intracellular levels of glucose-6-P and phosphocreatine in the extensor may be controlled, in part, by a factor (s) transported to the muscle by axoplasmic flow. Other metabolites known to change 5 days after denervation, namely glucose, glycogen, lactate, and α-ketoglutarate, were not altered in extensor and soleus muscles innervated by vinblastine-treated nerves. The activities of glucose-6-phosphate dehydrogenase and hexokinase increased in denervated extensor muscles, but not in denervated soleus muscles. Thus, metabolism in extensor muscles may be more readily altered after disruption of neural influences than is metabolism in soleus muscles. In contrast to denervation, exposure of sciatic nerves to vinblastine did not alter enzyme activities. These results provide evidence that certain metabolic processes, as well as membrane properties in skeletal muscle, are influenced by separate and distinct neural factors.

Changes of ribosomal capacity for protein synthesis, contraction and histochemical properties of muscle after implantation of fast nerve into denervated and into self-reinnervated slow soleus muscle of the rat.

The ribosomal capacity for protein synthesis in the fast extensor digitorum longus muscle of the rat is markedly higher than in the slow soleus muscle. Implantation of the "fast" peroneal nerve into the denervated or into the self-reinnervated soleus muscle results in transformation (increase) of capacity of isolated ribosomes for protein synthesis into that of the fast muscle type. The degree of transformation is higher after implantation into the self-reinnervated than into the denervated soleus muscle. A high degree of recovery of weight and tetanic tension output is recorded after the "fast" nerve implantation. The effect of transformation with respect to contraction properties is considerably more marked in the case of heteroinnervation of the denervated muscle and persists even after 5 months of heteroinnervation. Transformation of the histochemical muscle fibre pattern is also more pronounced after heteroinnervation of the denervated than self-reinnervated soleus muscle; the muscle acquires the fibre pattern of the fast extensor digitorum longus muscle. The acquisition of the reciprocal pattern of oxidative and glycolytic enzymes suggests that the activation of protein synthesis induced by the foreign "fast" nerve supply is coupled with the operation of specific RNA species.

Neural regulation of mammalian fast and slow muscle myosins: an electrophoretic analysis.

Mammalian nerves to fast and slow muscles have the remarkable property of changing the speed of contraction of muscles following cross-reinnervation. The biochemical basis of speed transformation is the change in myosin in ATPase activity. This paper provides electrophoretic evidence for structural changes in myosin from cross-reinnervated muscles. A method is described for the separation of intact fast and slow muscle myosins by polyacrylamide gel electrophoresis. This method utilizes the fact that ATP and its analogs prevent the formation of myosin polymers in low ionic strength buffers. In this system, normal fast muscle myosin has a higher electrophoretic mobility than slow muscle myosin. Normal rat soleus myosin has a major slow and a minor fast component due to two populations of muscle fibers. The same muscle cross-reinnervated by a fast muscle nerve shows only the fast component, The normal, homogeneous fast extensor digitorum longus muscle has only the electrophoretically fast myosin, but following cross-reinnervation it shows both fast and slow components. These results suggest that mammalian motor nerves can induce or suppress the expression of genes that code for fast and slow skeletal muscle myosins.

Neural regulation of muscle activation

The effects of temperature and repetitive stimulation on isometric twitch contractions of normal, self-innervated and cross-innervated fast extensor digitorum longus and slow soleus muscles of the rat were studied in situ. Normal and self-innervated extensor digitorum longus showed a 2-fold increase in twitch tension following either a train of 200 stimuli at 35 C (post-tetanic potentiation) or lowering of temperature from 35 C to 20 C (cooling potentiation), while under these conditions the twitch tensions of normal and self-innervated slow soleus fell by about 15%. Post-tetanic and cooling potentiation were virtually abolished in cross-innervated extensor digitorum longus but appeared in cross-innervated soleus. The degree of potentiation in these and control muscles was inversely proportional to contraction time. These experiments suggest that mammalian motor nerves exert a controlling influence on the degree of activation of skeletal muscle during a twitch. An hypothesis of the molecular mechanism of post-titanic and cooling potentiation is proposed. According to this hypothesis, neural regulation of muscle activation results from the transformation of myosin after nerve cross-union.