The resilience of the size principle in the organization of motor unit properties in normal and reinnervated adult skeletal muscles

Henneman's size principle relates the input and output properties of motoneurons and their muscle fibers to size and is the basis for size-ordered activation or recruitment of motor units during movement. After nerve injury and surgical repair, the relationship between motoneuron size and the number and size of the muscle fibers that the motoneuron reinnervates is initially lost but returns with time, irrespective of whether the muscles are self- or cross-reinnervated by the regenerated axons. Although the return of the size relationships was initially attributed to the recovery of the cross-sectional area of the reinnervated muscle fibers and their force per fiber, direct enumeration of the innervation ratio and the number of muscle fibers per motoneuron demonstrated that a size-dependent branching of axons accounts for the size relationships in normal muscle, as suggested by Henneman and his colleagues. This same size-dependent branching accounts for the rematching of motoneuron size and muscle unit size in reinnervated muscles. Experiments were carried out to determine whether the daily amount of neuromuscular activation of motor units accounts for the size-dependent organization and reorganization of motor unit properties. The normal size-dependent matching of motoneurons and their muscle units with respect to the numbers of muscle fibers per motoneuron was unaltered by synchronous activation of all of the motor units with the same daily activity. Hence, the restored size relationships and rematching of motoneuron and muscle unit properties after nerve injuries and muscle reinnervation sustain the normal gradation of muscle force during movement by size-ordered recruitment of motor units and the process of rate coding of action potentials. Dynamic modulation of size of muscle fibers and their contractile speed and endurance by neuromuscular activity allows for neuromuscular adaptation in the context of the sustained organization of the neuromuscular system according to the size principle.     

Axotomy of developing rat spinal motoneurons: Cell survival,soma size,muscle recovery,and the influence of testosterone

During the period of synapse elimination, motoneurons are impaired in their ability to generate or regenerate axonal branches: following partial denervation of their target muscle, young motoneurons do not sprout to nearby denervated fibers and after axonal injury, they fail to reinnervate the muscle. In the rat levator ani (LA) muscle, which is innervated by motoneurons in the spinal nucleus of the bulbocavernosus (SNB), synapse elemination ends relatively late in development and can be regulated by testosterone. We took advantage of this system to determine if the end of synapse elimination and the development of regenerative capabilities by motoneurons share a common mechanism, or, alternatively, if these two events can be dissociated in time. Axotomy on or before postnatal day 14 (P14) caused the death of SNB motoneurons. By P21, toward the end of synapse elimination in the LA muscle, SNB motoneurons had developed the ability to survive axonal injury. Altering testosterone levels by castration on P7 followed by 4 weeks of either testosterone propionate or control injections did not change the ability of SNB motoneurons to survive axonal injury during development, although these same treatments alter the time course of synapse elimination in the LA muscle. Thus, we dissociated the inability of SNB motoneurons to recover from axonal injury from their developmental elimination of synaptic terminals. We also measured the effect of early axotomy on motoneuronal soma size and on target muscle weight. Axotomy on P14 caused a long-lasting decrease in the soma size of surviving SNB motoneurons, whereas motoneurons axotomized on P28 recovered their normal soma size. Axotomy on or before P7 caused severe atrophy of the target muscles, matching the extensive loss of motoneurons. However, target muscle recovery after axotomy on P14 was as good as recovery after axotomy at later ages, despite greater motoneuronal death after axotomy on P14. This result may reflect an increase in motor unit size, a decrease in polyneuronal innervation by SNB motoneurons that survive axotomy on P14, or a combination of the two. © 1995 John Wiley & Sons, Inc.     

Muscle Plasticity During Sprouting and Reinnervation

SYNOPSIS. When peripheral nerves are cut, the axotomized nervesand denervated muscles undergo atrophic changes which are reversedonly when functional connections are remade in the periphery.The restored interaction completely reverses the effects ofaxotomy and denervation and leads to rematching of the sizeof the motoneuron, muscle unit force, speed and histochemicalproperties, according to the size principle. Differences inunit force and fatigue characteristics between motor unit typesare not fully restored in reinnervated muscles but do not obscuresize relationships between the motoneurons and their muscleunits. Although intact motoneurons will supply increased numbers ofmuscle fibers after partial nerve injuries, regenerating axonsappear to be limited in their ability to enlarge their muscleunits. Increased motor unit force in reinnervated slow motorunits is accounted for primarily by an increase in fiber diameter;fast motor units do not increase their mean force output. As a result of the rematching of muscle unit properties withthe size of the motoneurons that reinnervate them, motor unitproperties are appropriate for fine control of movement aftercomplete or partial nerve injuries. However, regenerating axonsdo not reinnervate their original muscle fibers and unless thefibers are injured close to the muscles, they often fail toreinnervate their original muscles. The mismatching of motorpools with inappropriate target muscles is probably the mainfactor responsible for poor recovery of motor function aftercomplete nerve injuries.     

Some physiological and biochemical features of striated muscles reinnervated by preganglionic sympathetic fibers

Skeletal muscle fibers can be reinnervated by motor cholinergic fibers, that is, functional connection can be achieved. However, functional connection implies not only the capacity of the nerve impulse to elicit a contractile response but also the capability of the reinnervating neurons to evoke particular modifications of the physiological and biological features of the muscles. In order to search for some of the modifications due to reinnervation by preganglionic sympathetic fibers, muscle contraction time was studied in three different preparations of adult cats: a) cricothyroid muscle reinnervated by preganglionic fibers; b) cricothyroideus reinnervated by its own nerve; and c) the corresponding normal neuromuscular preparation. The activities of malic dehydrogenase, of aldolase and pyruvic kinase were studied in these three preparations as well as in the denervated cricothyroid muscles. Reinnervation by preganglionic fibers prolonged the twich contraction time, whereas, self-reinnervation did not alter it. On the other hand, the activities of the three enzymes decreased as a result of denervation. In contrast, the muscle reinnervated with sympathetic preganglionic fibers partially recovered the normal level of malic dehydrogenase and the aldolase activities; but showed no modification in the level of pyruvic kinase activity. Conversely, in the muscle fibers reinnervated by their own nerve, the activity of the three enzymes returned to normal levels. The shortening of contraction time of the preganglionic reinnervated muscle correlates well with the features of the enzymic activities found in these muscles. It can be concluded: a) preganglionic sympathetic axons are able to achieve functional connections with striated muscles and b) considering the trophic effect, preganglionic fibers resemble the motor nerve supplying slow muscles.     

Lack of fiber type selectivity during reinnervation of neonatal rabbit soleus muscle

Fast and slow contracting fibers in neonatal mammalian skeletal muscle are each innervated in a highly specific manner by motor neurons of the corresponding type, even at an age when polyinnervation is widespread. Chemospecific recognition is a possible mechanism by which this pattern of innervation could be established. We have investigated this possibility by studying the degree of specificity during reinnervation of rabbit soleus muscle following nerve crush on Postnatal Day 1 or 4. We assayed fiber type composition by measuring the twitch rise times of motor units within 2 days of the onset of functional reinnervation (5-6 days after nerve crush). In contrast to the broad, bimodal distribution of single motor unit twitch rise times seen in normal muscles, motor units in reinnervated muscles yielded a narrower, unimodal distribution of rise times. Rise times of reinnervated units were intermediate to those of normal fast and slow units, suggesting that reinnervated units were composed of a mixture of fast and slow contracting fibers. An alternative possibility, that specific reinnervation was masked by contractile dedifferentiation of muscle fibers, was examined by maintaining a transmission blockade induced by botulinum toxin poisoning for an equivalent interval. Twitch rise times of treated motor units exhibited the distinctly bimodal distribution characteristic of normal muscles, suggesting that muscle fibers can retain contractile diversity during a transient period of denervation. We carried out computer simulations to estimate the amount of rise time diversity induced by varying degrees of specificity during reinnervation. Based on this analysis, we conclude that there is little if any selective reinnervation of muscle fiber types at the ages studied.     

Transplantation and transposition of skeletal muscles into the faces of monkeys

Restoration of normal facial movement after long-term facial paralysis with muscle atrophy has not yet been achieved reliably by either free grafts, in which fibers degenerate and regenerate, or by grafts made with microneurovascular repair, in which most fibers survive. Our purpose was to compare the structural and functional properties of free muscle grafts and continuously perfused muscle flaps transplanted into the faces of monkeys. In adult monkeys, the facial muscles were replaced by either a free graft of a donor muscle from the lower limb or a denervated flap of ipsilateral temporalis muscle. Each graft or flap was reinnervated with the preserved buccal branch of the facial nerve. The control muscles, grafts, and flaps were examined 90 days later for gross appearance, contractile properties, and fiber areas. Compared with muscle flaps, free grafts showed greater adaptability to the new location and innervation and a closer approximation to the structural and functional properties of the original facial musculature.     

Innervation of free muscle grafts in the rat in the absence of mechanical trauma to surrounding muscles or nerves.

Soleus muscles in the rat were freely grafted alongside a normal soleus muscle in the absence of mechanical trauma to any of the surrounding muscles or motor nerves. The object of this experiment was to determine whether or not the muscle grafts would become reinnervated under these circumstances. Contractile and histochemical properties of the grafts were compared with those of the contralateral denervated soleus as well as normal muscles. Innervation of the grafts did occur, and it was concluded that the innervation of the grafts arose primarily from sprouts from nerves supplying neighboring muscles. The grafts were studied with specific nerve stains, histochemical techniques and by analysis of their contractile properties.     

Réinnervation vagale sensitive et la composition du muscle sternocéphalique chez le lapin

The crossed nerve anastomosis between the peripheral end of the vagus nerve, cut above the nodose ganglion, and the peripheral end of the accessory nerve has demonstrated the capacity of some vagal afférents to reinnervate, via the accessory nerve stump, certain sternocephalicus muscle fibers in the rabbit. These results add to our understanding of the capacity of these afferents to counter the post-denervational atrophying process that occurs in the reinnervated muscles and to evaluate the changes induced in these muscles during reinnervation. Our work shows that within 3 months, the vagal sensory reinnervation of previously denervated sternocephalicus muscles induces their total weight recovery. This recovery is concomitant on the one hand with the hypertrophy of the four muscle fiber types (I, IIbd, IIc and IIa) identified histochemically in the normal muscles and, on the other, with the appearance of small newly formed myofibers, which are often underlined by characteristic central nuclei. The vagal sensory neurones induce important changes in the percentages and the muscle cross-sectional distribution of the fibers in reinnervated muscles. In these muscles we see also the disappearance of the fast myosin heavy chains MHCiib and MHCiid, the upholding of the fast MHCiia percentage and an increase in the slow MHCi isoform.     

Regeneration of reinnervated rat soleus muscle is accompanied by fiber transition toward a faster phenotype.

The functional recovery of skeletal muscles after peripheral nerve transection and microsurgical repair is generally incomplete. Several reinnervation abnormalities have been described even after nerve reconstruction surgery. Less is known, however, about the regenerative capacity of reinnervated muscles. Previously, we detected remarkable morphological and motor endplate alterations after inducing muscle necrosis and subsequent regeneration in the reinnervated rat soleus muscle. In the present study, we comparatively analyzed the morphometric properties of different fiber populations, as well as the expression pattern of myosin heavy chain isoforms at both immunohistochemical and mRNA levels in reinnervated versus reinnervated-regenerated muscles. A dramatic slow-to-fast fiber type transition was found in reinnervated soleus, and a further change toward the fast phenotype was observed in reinnervated-regenerated muscles. These findings suggest that the (fast) pattern of reinnervation plays a dominant role in the specification of fiber phenotype during regeneration, which can contribute to the long-lasting functional impairment of the reinnervated muscle. Moreover, because the fast II fibers (and selectively, a certain population of the fast IIB fibers) showed better recovery than did the slow type I fibers, the faster phenotype of the reinnervated-regenerated muscle seems to be actively maintained by selective yet undefined cues.     

Influence of overload on recovery of rat plantaris from partial denervation

A functional index of neural adaptability is the capacity of motoneurons to extend and establish supernumerary connections with neighboring denervated muscle fibers. The purpose of this study was to guage this response in rat plantaris muscles subjected to increased levels of activity resulting from the surgical removal of the synergistic gastrocnemius and soleus muscles. Thirty-seven days of overload increased plantaris absolute (69%) and relative (82%) weight, whole muscle (35%) and individual fiber (37%) mean cross-sectional area, half-relaxation time (1/2RT; 25%), and maximum tetanic tension (P0; 21%). In a separate group of animals that had undergone 30 days of overload, three-quarters of the plantaris muscle fibers were denervated by sectioning radicular nerve L4. At 7 days postlesion, contractile responses were obtained from sprouting motor units remaining in radicular nerve L5, and the results compared to a nonoverloaded group that had undergone this same procedure. Twitch time to peak tension and 1/2RT were prolonged in normal partially denervated (PD) and overloaded partially denervated (OPD) muscles, and this response was significantly greater in the overloaded muscles. Both PD and OPD muscles increased twitch tension (38%) and peak tension developed at 25 Hz (34%) to a similar extent, during recovery from partial denervation. These increases, attributable to sprouting of L5 motor axon collaterals, were matched in PD muscles with a corresponding increase in P0, a response which did not occur in OPD muscles. Additionally, a more extensive decrease in P0 occurred as a result of partial denervation in OPD muscles compared with whole muscle P0 of nondenervated muscle (L4 plus L5 stimulation).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential delay of reinnervating axons alters specificity in the rat serratus anterior muscle

Previous studies have shown remarkable rostrocaudal selectivity by regenerating motoneurons to the rat serratus anterior (SA) muscle after freezing, crushing, or sectioning the long thoracic (LT) nerve. The LT nerve contains motoneurons from both the sixth and seventh cervical spinal nerves (C6 and C7), with C6 motoneurons as the major source of innervation throughout the muscle, and with C7 motoneurons innervating a larger percentage of muscle fibers caudally than rostrally. To determine if synaptic competition can play a role in neuromuscular topography, both the LT nerve and the branch carrying C6 (rostral) motoneurons to the LT nerve were crushed in newborn rats. This approach provides a temporal advantage to regenerating C7 (caudal) motoneurons. After an initial period during which C7 motoneurons reinnervated a larger proportion of muscle fibers than normal in all SA muscle sectors, C6 motoneurons regained their original proportion of rostral muscle fibers. Caudally, however, C7 motoneurons maintained an expanded territory. With this two-site crush method, the number of C6 motoneurons that reinnervate the SA muscle was significantly decreased from normal, whereas the number of C7 motoneurons remained the same. It is concluded that when C7 motoneurons are given a temporal advantage, synaptic specificity can be altered transiently in rostral muscle sectors and permanently in caudal sectors, and this is correlated with a disproportionate loss of C6 motoneurons. Moreover, this may be an important model for studies of synaptic competition, where terminals destined to be eliminated can be identified beforehand. © 1995 John Wiley & Sons, Inc.     

The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: II. Functional evaluation of reinnervated muscle.

Isometric contractile function was evaluated in primates receiving peripheral nerve allografts and autografts. Twelve adult male cynomolgus monkeys received both sural nerve allografts and autografts to the ulnar nerve in opposite forearms. Half the animals received Cyclosporin A (CsA) immunosuppression (25 mg/kg per day); the remaining animals received placebo. One year following nerve engraftment, isometric contractile muscle function was evaluated in reinnervated abductor digiti quinti and intact abductor pollicis brevis muscles. Maximal twitch tension (Pt), tetanic tension (P(o)), time to peak tension (tpt), rate of rise of twitch tension (DP/dt), and muscle fatigue were evaluated at optimal muscle length (L(o)). All reinnervated muscles distal to nerve autografts and allografts in both Cyclosporin A-immunosuppressed and placebo-treated animals generated equivalent maximal twitch tension, tetanic tension, and time to peak tension, with no significant difference between groups (p > 0.05 by ANOVA). There was a tendency toward increased muscle fatiguability in Cyclosporin A-treated animals (p > 0.05). However, the rate of rise of twitch tension was significantly faster in the reinnervated and intact muscles of Cyclosporin A-treated primates (p < 0.05). Evidence of excellent functional reinnervation across nerve allografts and autografts similar to that seen in histologic and electrophysiologic studies was noted. Cyclosporin A immunosuppression did not significantly enhance recovery of muscle function distal to nerve allografts in this model.     

Contractile Properties and Movement Behaviour in Neonatal Rats with Axotomy, treated with the NMDA Antagonist DAP5

ABSTRACT: BACKGROUND: It is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury. METHODS: Wistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (normal saline injection), b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months). RESULTS: 1. Administration of DAP5 alone did not provoke any side-effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p<0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their kinetic behaviour were significantly improved compared to axotomized ones (p<0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p<0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p<0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles. CONCLUSIONS: Our results confirm that contractile properties and kinetic behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.     

Plasticity in mammalian skeletal muscle.

While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins.     

Development of rat muscle during short- and long-term hindlimb suspension

Histochemical and contractile properties of developing rat soleus (Sol) and plantaris (P) muscles were studied after hindlimb suspension to determine the effects of reduced activity levels on muscle development. Suspension (S) began at age 18 days and lasted for 14, 28, and 206 days, and results were compared with age-matched controls. Body weights were normal until 14 days and Sol growth was inhibited more than P, weighing 38 and 47% of controls at 46 and 224 days compared with 68 and 59% in P. The Sol did not develop into a slow-twitch (ST) muscle as evidenced by faster times to peak tension and half-relaxation times, faster times to develop 50% of maximum tetanic tension (Po) and a mean of 33% fewer ST fibers. Twitch tension and Po were lower in S-Sol and S-P, but force/cross-sectional area was unchanged. Fiber areas were smaller, but no structural changes characteristic of disuse atrophy were found. Fiber type populations were unchanged in P, and contractile properties were only minimally affected, demonstrating the greater importance of activity for ST muscles during development.     

Beta2-adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury.

Beta(2)-adrenoceptor agonists such as fenoterol are anabolic in skeletal muscle, and because they promote hypertrophy and improve force-producing capacity, they have potential application for enhancing muscle repair after injury. No previous studies have measured the beta(2)-adrenoceptor population in regenerating skeletal muscle or determined whether fenoterol can improve functional recovery in regenerating muscle after myotoxic injury. In the present study, the extensor digitorum longus (EDL) muscle of the right hindlimb of deeply anesthetized rats was injected with bupivacaine hydrochloride, which caused complete degeneration of all muscle fibers. The EDL muscle of the left hindlimb served as the uninjured control. Rats received either fenoterol (1.4 mg x kg(-1) x day(-1)) or an equal volume of saline for 2, 7, 14, or 21 days. Radioligand binding assays identified a approximately 3.5-fold increase in beta(2)-adrenoceptor density in regenerating muscle at 2 days postinjury. Isometric contractile properties of rat EDL muscles were measured in vitro. At 14 and 21 days postinjury, maximum force production (P(o)) of injured muscles from fenoterol-treated rats was 19 and 18% greater than from saline-treated rats, respectively, indicating more rapid restoration of function after injury. The increase in P(o) in fenoterol-treated rats was due to increases in muscle mass, fiber cross-sectional area, and protein content. These findings suggest a physiological role for beta(2)-adrenoceptor-mediated mechanisms in muscle regeneration and show clearly that fenoterol hastens recovery after injury, indicating its potential therapeutic application.     

Effects of tetrodotoxin-induced disuse on properties of developing rat gastrocnemius muscle

Our goal was to determine the influence of a complete lack of neuromuscular activity, during a period of rapid muscle growth, on muscle morphology and contractile function. Rats, 21 days old, had one hindlimb paralyzed for a period of 7-9 consecutive days by repetitive implantation of a silastic cuff containing tetrodotoxin (TTX), a specific nerve impulse conduction blocker, around the sciatic nerve. In situ isometric contractile properties of gastrocnemius were measured at 31 days of age, and muscles were subsequently examined histologically. Normal growth during this period resulted in a two- to three-fold increase in muscle weights, mean muscle fiber cross-sectional areas and increases in absolute twitch and tetanic tensions. After inactivity from 21 to 30 days of age, gastrocnemius muscles were smaller, and tetanically weaker, than age-matched controls. The normal cross-sectional area increase of fast-twitch fibers was preferentially affected. Inactive muscles also demonstrated significantly slower twitch responses, had higher twitch:tetanus ratios and relative tensions at 25 Hz than age-matched controls, suggesting a "slower" contractile response. On the other hand, maximum rate of tetanic tension development was elevated. These effects of inactivity appeared to be reversed by resumption of normal activity for 4 days. Neuromuscular inactivity during a relatively short period of rapid muscle growth causes significant muscle morphological and contractile changes, which are most likely reversible.     

Length-tension relationships are altered in regenerating muscles of the rat after bupivacaine injection.

Intramuscular injection of bupivacaine causes complete degeneration of fibers in extensor digitorum longus (EDL) muscles of rats, followed by complete regeneration within 60 days. Previous studies have shown that regenerated EDL muscles are protected from contraction-induced injury 60 days after bupivacaine injection. It is possible that these regenerated muscles have altered length-tension relations because of fiber remodeling. We tested the hypothesis that length-tension relations are different in bupivacaine-injected and noninjected control muscles. EDL and soleus muscles of the right hindlimb of deeply anesthetized rats were injected with bupivacaine and then allowed to recover for 7, 14, 21, or 60 days (7D, 14D, 21D, 60D), and isometric contractile properties were assessed. Muscles of the contralateral limb were not injected and served as control. EDL muscles recovered from bupivacaine injection more rapidly than soleus muscles, with mass restored to control levels at 21D, and isometric tetanic force (P(o)) restored to control at 60D. In contrast, mass and P(o) of injected soleus muscles was not restored to control even at 60D. In 7D EDL muscles, length-tension curves were shifted leftward compared with control, but in 21D and 60D EDL muscles length-tension curves were right shifted significantly (treatment x muscle length: P < 0.001). Although no clear shift in the position of the length-tension curve was observed in regenerating soleus muscles, force production was enhanced on the descending limb of the curve in 60D soleus muscles (treatment x relative muscle length: P < 0.01). The rightward shift in the length-tension curve of EDL muscles 60 days after bupivacaine injection is likely to contribute to the mechanism for their previously observed protection from contraction-induced injury.     

Motoneuron and muscle fiber succinate dehydrogenase activity in control and overloaded plantaris.

To determine the level of coordination in succinate dehydrogenase (SDH) activity between plantaris motoneurons and muscle fibers, the soleus and gastrocnemius muscles were bilaterally excised in four cats to subject the plantaris to functional overload (FO). Five normal cats served as controls. Twelve weeks after surgery the right plantaris in each cat was injected with horseradish peroxidase to identify plantaris motoneurons. SDH activity then was measured in a population of plantaris motoneurons and muscle fibers in each cat. Control motoneurons and muscle fibers had similar mean SDH activities and a similar relationship between cell size and SDH activity. After FO, muscle fiber size doubled and mean muscle fiber SDH activity halved. Motoneuron mean SDH activity and size were unaffected by FO. Total SDH activity was unchanged in both the motoneurons and muscle fibers after FO. These changes suggest a selective increase in contractile proteins with little or no modulation of mitochondrial proteins in the muscle fibers, because total SDH activity was unchanged in muscle fibers after FO. These data demonstrate that although mean SDH activities were similar in control motoneurons and muscle fibers, mean SDH activities in these two cell types can change independently.     

Skeletal muscle fiber regeneration following heterotopic autotransplantation in cats.

Whole 3 g extensor digitorum longus (EDL) muscles of cats were autotransplanted. The EDL muscles were either transplanted without denervation prior to transplantation (normal transplants) or denervated 3 to 4 weeks prior to transplantation (pre-denervated transplants). A few peripheral skeletal muscle fibers survived transplantation but most fibers degenerated and then regenerated as the transplant became revascularized. Both normal and pre-denervated muscles regenerated successfully and by 50 days after transplantation fibers which had reinnervated showed high and low myofibrillar ATPase activity. Compared to controls, the smaller mean fiber cross-sectional area of the transplants was due to the large number of small fibers, but some fibers in the transplant were larger than any fibers observed in the controls. Transplants regained 57 percent of the muscle mass of the controls. Contraction and half relaxation times of transplanted muscles were slower than controls, but peak isometric tetanus tension per cm² of muscle was nearly normal. Fifty to 170 days after transplantation, muscles showed low oxidative capacity and fatigued rapidly.