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.     

Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle

Reasons for the progressive age-related loss of skeletal muscle mass and function, namely sarcopenia, are complex. Few studies describe sarcopenia in mice, although this species is the mammalian model of choice for genetic intervention and development of pharmaceutical interventions for muscle degeneration. One factor, important to sarcopenia-associated neuromuscular change, is myofibre denervation. Here we describe the morphology of the neuromuscular compartment in young (3 month) compared to geriatric (29 month) old female C57Bl/6J mice. There was no significant difference in the size or number of motoneuron cell bodies at the lumbar level (L1-L5) of the spinal cord at 3 and 29 months. However, in geriatric mice, there was a striking increase (by ～2.5 fold) in the percentage of fully denervated neuromuscular junctions (NMJs) and associated deterioration of Schwann cells in fast extensor digitorum longus (EDL), but not in slow soleus muscles. There were also distinct changes in myofibre composition of lower limb muscles (tibialis anterior (TA) and soleus) with a shift at 29 months to a faster phenotype in fast TA muscle and to a slower phenotype in slow soleus muscle. Overall, we demonstrate complex changes at the NMJ and muscle levels in geriatric mice that occur despite the maintenance of motoneuron cell bodies in the spinal cord. The challenge is to identify which components of the neuromuscular system are primarily responsible for the marked changes within the NMJ and muscle, in order to selectively target future interventions to reduce sarcopenia.     

Neural Regulation of Muscle Glucose 6-Phosphate Dehydrogenase: Effect of Batrachotoxin and Tetrodotoxin

Abstract: We tested the hypothesis that glucose 6-phosphate dehydrogenase (G6PD) activity in the rat skeletal muscle is regulated by putative axonally derived neurotrophic factors. This was accomplished by comparing the effects of nerve section and subperineural injection of batrachotoxin (BTX) or tetrodotoxin (TTX) on G6PD in rat extensor digitorum longus (EDL) muscle. BTX, an agent known to block nerve impulse conduction and axonal transport, increased G6PD activity to 155% and 163% of control by days 2 and 4 after injection. Denervation of the EDL muscle by section of the peroneal nerve 10–20 mm from its entrance to the muscle caused G6PD activity to increase to 170% of control by day 1 and to 200% and 180% of control by days 2 and 4, respectively. The increase in enzyme activity after denervation and after subperineural injection of BTX was due in part to muscle inactivity resulting from blockade of nerve impulses. This conclusion is based upon the observation that subperineural injection of TTX at an identical site in the peroneal nerve caused a small but significant (30%) increase in G6PD activity after 4 days. Choline acetyltransferase (CAT) activity was assessed as a measure of the efficacy of blockade of slow axonal transport. Decreases in CAT activity following denervation or injection of BTX or TTX were parallel to increases in G6PD activity observed under these conditions. These results argue for a role of axonal transport in neural regulation of muscle G6PD, with a small contribution by neuromuscular activity.     

Differential Effect of Denervation on Free-Radical Scavenging Enzymes in Slow and Fast Muscle of Rat

To determine the effect of denervation on the free-radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the midthigh region and the muscle tissue levels of five enzymes were studied 2 and 5 weeks following crush. Recently developed radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. Total tissue content of cuprozinc superoxide dismutase showed a mild decrease after denervation in slow but not in fast muscle. Manganosuperoxide dismutase and fumarase decreased markedly at 2 weeks and returned toward control levels by 5 weeks, the changes appearing to be greater in slow than in fast muscle. At 2 weeks, cytochrome c oxidase decreased significantly in slow, but not in fast muscle. GSH-peroxidase at baseline was 10-fold higher in slow than in fast muscle, markedly decreased at 2 weeks in slow muscle, and returned toward control levels at 5 weeks, whereas the total enzyme activity in fast muscle did not change through 5 weeks. These data represent the first systematic report of free radical scavenging systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.     

Responses of motor and sensory neurons of rodents to spaceflight

Spinal motoneurons innervating skeletal muscles comprised predominantly of high oxidative fibers, i.e. slow oxidative and fast oxidative glycolytic, have higher oxidative enzyme activities than motoneurons innervating skeletal muscles comprised primarily of low oxidative fibers, i.e. fast glycolytic. These findings suggest that there is a close relationship between the oxidative phosphorylation capacity of a motoneuron and of the muscle fibers that it innervates. Since some skeletal muscles become faster and less oxidative after 4-14 days of spaceflight, it might be expected that oxidative enzyme activities in some motoneurons also may decrease after spaceflight. In addition, there is significant muscular atrophy after even short spaceflights and, therefore, it may be expected that some motoneurons associated with these muscles also would atrophy. In the present paper, we examine the issue of whether spaceflight induces changes in the oxidative enzyme activity and/or size of spinal motoneurons.     

Activity dependent characteristics of fast and slow muscle: biochemical and histochemical considerations

The effects of denervation and hindlimb suspension induced disuse on concentrations of ATP, phosphocreatine (PC), and fiber type profile were investigated in slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles. The results show that the soleus and EDL muscles differ in their dependency on loadbearing as a stimulus for maintaining normal energy metabolism and the biochemical and morphological characteristics of muscle fibers. As determined by R-P methodology, suspension reduced ATP and PC concentrations of the soleus to 26% and 56%, respectively, while, in EDL only, PC is reduced to 71% of control with no change in ATP. Both muscles, however, show identical losses in ATP and PC following denervation. The energy charge, an indicator of Pi availability in muscle was reduced significantly in both denervated muscles to 82% and 85% in soleus and EDL, respectively. No significant reduction of the energy charge was seen in the muscles from suspended rats. Thus, in parallel with the indirect regulation through muscle loadbearing, the nerve can effectively modulate the levels of high-energy phosphates more directly by some regulatory mechanisms independent of muscle type. Denervation and suspension disuse increased the proportion of type 2 fibers in the soleus with a concomitant decrease in type 1 fibers and a relative rise in the number of very small diameter fibers. The EDL showed only variation in fiber size.     

Effects of hindlimb suspension on soleus muscle fibers and their spinal motoneurons in Wistar Hannover rats

Cross-sectional areas and succinate dehydrogenase (SDH) activities of soleus muscle fibers and their spinal motoneurons in male Wistar Hannover rats were determined after 16 days of hindlimb suspension. A decreased percentage of type I fibers and an increased percentage of type I+II fibers were observed after hindlimb suspension. Cross-sectional areas of all types of fibers were smaller in the hindlimb suspended than control rats. SDH activities of all types of fibers did not change after hindlimb suspension. Numbers, cross-sectional areas, or SDH activities of spinal motoneurons did not change after hindlimb suspension. It is suggested that spinal motoneurons innervating the rat soleus muscle are not affected by decreased neuromuscular activity on Earth and that gravity itself is important for maintaining of spinal motoneuron metabolic properties.     

The regulation of intramuscular nerve branching during normal development and following activity blockade

In vertebrates, approximately 50% of the lumbosacral motoneurons die during a short period of development that coincides with synaptogenesis in the limb. Although it has been postulated that these motoneurons die because they fail to obtain adequate trophic support from the muscles, it is not clear how this factor is supplied. The mechanism by which activity blockade prevents motoneurons cell death is also unknown. In order to begin to understand the nature of these proposed trophic interactions, we have examined the temporal sequence of axonal invasion and ramification within two muscles of the chick hindlimb, the predominantly slow iliofibularis and the fast posterior iliotibialis, during the cell death period. We found striking differences in intramuscular nerve ingrowth and branching between fast and slow muscle. We also observed differences in the molecular composition of fast and slow myotubes that may contribute to the nerve pattern differences. In addition, we observed a progressive increase in the degree of intramuscular nerve fasciculation as well as a precise temporal sequence of nerve branching. The earliest detectable response to chronic curarization was a dramatic decrease in the degree of intramuscular nerve fasciculation. Activity blockade also greatly enhanced nerve branching within the muscles from the time that nerve branches normally formed, and, additionally, interfered with the normal cessation of axon growth. Our results support the idea that nerve endings are the sites of trophic uptake. Furthermore, although our results do not allow us to exclude other activity-dependent influences on motoneuron survival, they suggest the following testable hypotheses: (1) the normal regulation of motoneuron survival may result from the precise control of intramuscular nerve branching, (2) activity blockade may increase motoneuron survival by enhancing intramuscular nerve branching, and (3) anything which affects this complex process of nerve branching may also alter motoneuron survival.     

Reinnervation of murine muscle following fetal sciatic nerve transection

A technique is reproted that permits transection of the sciatic nerve of mouse fetuses without interfering with fetal viability. Sciaticotomy was performed on Swiss Webster mice at day 17 of gestation; the contralateral side served as a control. Six weeks later the extensor digitorum longus (EDL) muscles on both sides were injected with horseradish peroxidase (HRP). Examination of the lumbar spinal cord revealed that while a substantial number of motor neurons in the region of the spinal cord giving rise to the sciatic nerve died, the EDL muscle did become reinnervated. The size of the EDL motor neuron pool on the denervated-reinnervated side was ～43% of that seen on the control side. While the control EDL motor neuron pool was located in lumbar segments L3–L5, the location of the pool to the denervated-reinnervated EDL was shifted cranially to L2–L4. Denervated-reinnervated EDL muscles were analyzed immunohistochemically to study the effect of fetal denervation on the neuronal cell adhesion molecule (N-CAM) expression. At 2 weeks postnatal, N-CAM immunoreactivity in control muscle was segregated to the motor end plate region, while fetally denervated muscle continued to express N-CAM along the length of the sarcolemma. Thus fetally denervated muscle does not develop the same pattern of N-CAM expression as normal, innervated muscle. By 6 weeks of age, the denervated-reinnervated muscle showed the same level and distribution of N-CAM immunoreactivity as did age-matched control muscle, indicating that most, if not all, of its myofibers had been reinnervated.     

Reinnervation of murine muscle following fetal sciatic nerve transection.

A technique is reported that permits transection of the sciatic nerve of mouse fetuses without interfering with fetal viability. Sciaticotomy was performed on Swiss Webster mice at day 17 of gestation; the contralateral side served as control. Six weeks later the extensor digitorum longus (EDL) muscles on both sides were injected with horseradish peroxidase (HRP). Examination of the lumbar spinal cord revealed that while a substantial number of motor neurons in the region of the spinal cord giving rise to the sciatic nerve died, the EDL muscle did become reinnervated. The size of the EDL motor neuron pool on the denervated-reinnervated side was approximately 43% of that seen on the control side. While the control EDL motor neuron pool was located in lumbar segments L3-L5, the location of the pool to the denervated-reinnervated EDL was shifted cranially to L2-L4. Denervated-reinnervated EDL muscles were analyzed immunohistochemically to study the effect of fetal denervation on the neuronal cell adhesion molecule (N-CAM) expression. At 2 weeks postnatal, N-CAM immunoreactivity in control muscle was segregated to the motor end-plate region, while fetally denervated muscle continued to express N-CAM along the length of the sarcolemma. Thus fetally denervated muscle does not develop the same pattern of N-CAM expression as normal, innervated muscle. By 6 weeks of age, the denervated-reinnervated muscle showed the same level and distribution of N-CAM immunoreactivity as did age-matched control muscle, indicating that most, if not all, of its myofibers had been reinnervated.     

Interactions between spinal cord stimulation and activity blockade in the regulation of synaptogenesis and motoneuron survival in the chick embryo

The present study investigated the effects of spinal cord stimulation, neuromuscular blockade, or a combination of the two on neuromuscular development both during and after the period of naturally occurring motoneuron death in the chick embryo. Electrical stimulation of the spinal cord was without effect on motoneuron survival, synaptogenesis, or muscle properties. By contrast, activity blockade rescued motoneurons from cell death and altered synaptogenesis. A combination of spinal cord stimulation and activity blockade resulted in a marked increase in motoneuron death, and also altered synaptogenesis similar to that seen with activity blockade alone. Perturbation of normal nerve–muscle interactions by activity blockade may increase the vulnerability of developing motoneurons to excessive excitatory afferent input (spinal cord stimulation) resulting in excitotoxic-induced cell death. © 1993 John Wiley & Sons, Inc.     

Influence of denervation on the molecular forms of junctional and extrajunctional acetylcholinesterase in fast and slow muscles of the rat.

Acetylcholinesterase (AChE) molecular forms in denervated rat muscles, as revealed by velocity sedimentation in sucrose gradients, were examined from three aspects: possible differences between fast and slow muscles, response of junctional vs extrajunctional AChE, and early vs late effects of denervation. In the junctional region, the response of the asymmetric AChE forms to denervation is similar in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle: (a) specific activity of the A12 form decreases rapidly but some persists throughout and even increases after a few weeks; (b) an early and transient increase of the A4 AChE form lasting for a few weeks may be due to a block in the synthetic process of the A12 form. In the extrajunctional regions, major differences with regard to AChE regulation exist already between the normal EDL and SOL muscle. The extrajunctional asymmetric AChE forms are absent in the EDL because they became completely repressed during the first month after birth, but they persist in the SOL. Differences remain also after denervation and are, therefore, not directly due to different neural stimulation patterns in both muscles: (a) an early but transient increase of the G4 AChE occurs in the denervated EDL but not in the SOL; (b) no significant extrajunctional activity of the asymmetric AChE forms reappears in the EDL up till 7 wk after denervation. In the SOL, activity of the asymmetric AChE forms is decreased early after denervation but increases thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased effectiveness of a motorneuron after partial denervation of its target muscle in the cricket Teleogryllus oceanicus

Fibers of the metathoracic extensor tibia muscle of the cricket Teleogryllus oceanicus are innervated by a slow excitatory axon (slow fibers), a fast excitatory axon (fast fibers), or by both slow and fast axons (dual fibers). Sectioning metathoracic nerve 5 removes the fast axon input to the muscle but not that of the slow axon. Following such partial denervation, the mechanical responses initiated by the slow axon increase progressively for at least 30 days; twitch tensions reach 5–10 times those of control muscles and tetanic tensions 10–30 times control values. After sectioning nerve 5, resting membrane potentials decrease in those fibers which originally received fast axon input and the input resistance of all fiber types increases, including that of slow fibers which are not innervated through nerve 5. Excitatory junctional potentials (EJPs) initiated by the slow axon become larger following partial denervation, accounting in part for the larger contraction amplitudes. The increased input resistance is adequate to account for the larger EJPs in slow fibers but not for the proportionally greater increase in EJP amplitude in fibers which were formerly dually innervated. The change in EJP amplitude is abrupt in slow fibers and gradual in formerly dual fibers.     

Nerve injury affects the capillary supply in rat slow and fast muscles differently

The goal of this study was to determine the acute effects of permanent denervation on the length density of the capillary network in rat slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles and the effect of short-lasting reinnervation in slow muscle only. Denervation was performed by cutting the sciatic nerve. Both muscles were excised 2 weeks later. Reinnervation was studied 4 weeks after nerve crush in SOL muscle only. Capillaries and muscle fibres were visualised by triple immunofluorescent staining with antibodies against CD31 and laminin and with fluorescein-labelled Griffonia (Bandeira) simplicifolia lectin. A recently developed stereological approach allowing the estimation of the length of capillaries adjacent to each individual fibre (Lcap/Lfib) was employed. Three-dimensional virtual test grids were applied to stacks of optical images captured with a confocal microscope and their intersections with capillaries and muscle fibres were counted. Interrelationships among capillaries and muscle fibres were demonstrated with maximum intensity projection of the acquired stacks of optical images. The course of capillaries in EDL seemed to be parallel to the fibre axes, whereas in SOL, their preferential direction deviated from the fibre axes and formed more cross-connections among neighbouring capillaries. Lcap/Lfib was clearly reduced in denervated SOL but remained unchanged in EDL, although the muscle fibres significantly atrophied in both muscle types. When soleus muscle was reinnervated, capillary length per unit fibre length was completely restored. The physiological background for the different responses of the capillary network in slow and fast muscle is discussed. This study was supported by the Slovenian Research Agency and the Ministry of Education, Youth and Sport of the Czech Republic (KONTAKT grant no. 19/2005).     

Myogenic and neurogenic contributions to the development of fast and slow twitch muscles in rat.

The histochemical ATPase activity and the myosin light chains of a rat fast muscle (extensor digitorum longus, EDL) and a rat slow muscle (soleus) during development have been investigated. Both muscles initially synthesize fast myosin light chains and show the intense histochemical ATPase activity characteristic of adult fast muscle fibers. After birth, the soleus begins to accumulate slow fibers with their characteristic low histochemical ATPase activity, and slow myosin light chains begin to appear. Sciatic neurectomy prevents the development of slow fibers and the synthesis of slow myosin light chains in the soleus, while the EDL is unaffected. Similarly, cordotomy of an adult rat results, in the soleus, in the appearance of fibers with more intense staining for ATPase and an increase in fast myosin light chains. The EDL is unchanged by cordotomy. As a result, we suggest that slow muscle development, but not fast muscle development, is dependent upon the functional activity of the nervous system.     

Slow myosin in developing rat skeletal muscle

Through S1 nuclease mapping using a specific cDNA probe, we demonstrate that the slow myosin heavy-chain (MHC) gene, characteristic of adult soleus, is expressed in bulk hind limb muscle obtained from the 18-d rat fetus. We support these results by use of a monoclonal antibody (mAb) which is highly specific to the adult slow MHC. Immunoblots of MHC peptide maps show the same peptides, uniquely recognized by this antibody in adult soleus, are also identified in 18-d fetal limb muscle. Thus synthesis of slow myosin is an early event in skeletal myogenesis and is expressed concurrently with embryonic myosin. By immunofluorescence we demonstrate that in the 16-d fetus all primary myotubes in future fast and future slow muscles homogeneously express slow as well as embryonic myosin. Fiber heterogeneity arises owing to a developmentally regulated inhibition of slow MHC accumulation as muscles are progressively assembled from successive orders of cells. Assembly involves addition of new, superficial areas of the anterior tibial muscle (AT) and extensor digitorum longus muscle (EDL) in which primary cells initially stain weakly or are unstained with the slow mAb. In the developing AT and EDL, expression of slow myosin is unstable and is progressively restricted as these muscles specialize more and more towards the fast phenotype. Slow fibers persisting in deep portions of the adult EDL and AT are interpreted as vestiges of the original muscle primordium. A comparable inhibition of slow MHC accumulation occurs in the developing soleus but involves secondary, not primary, cells. Our results show that the fate of secondary cells is flexible and is spatially determined. By RIA we show that the relative proportions of slow MHC are fivefold greater in the soleus than in the EDL or AT at birth. After neonatal denervation, concentrations of slow MHC in the soleus rapidly decline, and we hypothesize that, in this muscle, the nerve protects and amplifies initial programs of slow MHC synthesis. Conversely, the content of slow MHC rises in the neonatally denervated EDL. This suggests that as the nerve amplifies fast MHC accumulation in the developing EDL, accumulation of slow MHC is inhibited in an antithetic fashion. Studies with phenylthiouracil-induced hypothyroidism indicate that inhibition of slow MHC accumulation in the EDL and AT is not initially under thyroid regulation. At later stages, the development of thyroid function plays a role in inhibiting slow MHC accumulation in the differentiating EDL and AT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Primary cultures of endothelial cells of the rat liver

Summary In the soleus muscle of the normal rat the number of cells containing fast troponin I decreased and those containing slow troponin I increased after birth until less than 10% stained for the fast form in the adult muscle. On denervation of soleus muscle this pattern of change was reversed with the result that the majority of cells stained for fast troponin I. The change was more rapid when denervation was carried out at 12 weeks rather than at 52 weeks of age. Denervation of extensor digitorum longus and tibialis anterior muscles produced little change in the distribution of fast and slow troponin I over a period of 12 weeks. After long periods (>24 weeks) of denervation of these fast muscles, fast troponin I was observed in cells in which originally only slow troponin I could be detected. Similar results to those obtained with troponin I in both fast and slow muscles were obtained using antibodies to the fast and slow forms of troponin C and troponin T.     

The 21-Aminosteroid U-74389F Attenuates Hyperexpression of GAP-43 and NADPH-Diaphorase in the Spinal Cord of Wobbler Mouse,a Model for Amyotrophic Lateral Sclerosis

The wobbler mouse suffers an autosomal recessive mutation producing severe neurodegeneration and astrogliosis in spinal cord. It has been considered a model for amyotrophic lateral sclerosis. We have studied in these animals the expression of two proteins, the growth-associated protein (GAP-43) and the NADPH-diaphorase, the nitric oxide synthesizing enzyme, employing immunocytochemistry and histochemistry. We found higher expression of GAP-43 immunoreactivity in dorsal horn, Lamina X, corticospinal tract and ventral horn motoneurons in wobbler mice compared to controls. Weak NADPH-diaphorase activity was present in control motoneurons, in contrast to intense labeling of the wobbler group. No differences in diaphorase activity was measured in the rest of the spinal cord between control and mutant mice. A group of animals received subcutaneously for 4 days a 50 mg pellet of U-74389F, a glucocorticoid-derived 21-aminosteroid with antioxidant properties but without glucocorticoid activity. U-74389F slightly attenuated GAP-43 immunostaining in dorsal regions of the spinal cord from wobblers but not in controls. However, in motoneurons of wobbler mice number of GAP-43 immunopositive neurons, cell processes and reaction intensity were reduced by U-74389F. The aminosteroid reduced by 50% motoneuron NADPH-diaphorase activity. Hyperexpression of GAP-43 immunoreactivity in wobbler mice may represent an exaggerated neuronal response to advancing degeneration or muscle denervation. It may also be linked to increased nitric oxide levels. U-74389F may stop neurodegeneration and/or increase muscle trophism and stop oxidative stress, consequently GAP-43 hyperexpression was attenuated. Wobbler mice may be important models to evaluate the use of antioxidant steroid therapy with a view to its use in human motoneuron disease.     

Restoration of muscle contractile properties after partial and complete denervation

The subject of this experimental study was the isometric contractile properties of rat tibialis anterior muscle, number and average size of the motor units as well as type content and type-grouping of muscle fibres according to SDH activity in the same muscle after total and partial denervation (crushing the sciatic nerve and L4). It has been shown that in the process of reinnervation after total and partial denervation, quantitative differences with the general tendency in the dynamics of restoration of contractile properties of the whole muscle are found at different dynamics of restoration of electromyographic and muscle histochemical characteristics of motor units.     

Regulation of Taurine Transport in Rat Skeletal Muscle

Taurine concentration of soleus muscle (SL, slow-twitch) was initially about twofold higher than that of extensor digitorum longus muscle (EDL, fast-twitch). Taurine concentration in gastrocnemius muscle (GC) was intermediate between that of EDL and SL. Four days after sciatic nerve section, taurine concentration in the EDL but not in the SL was increased by 2.5-fold. The increase was not due to the muscle atrophy and was observed 28 days after denervation. Tenotomy did not increase the total taurine content of the EDL. The increase in taurine concentration of the denervated EDL was prevented by simultaneous ingestion of guanidinoethane sulfonate, a competitive inhibitor of taurine transport. The initial and the maximal rates of [3H]taurine uptake were significantly higher in SL than in EDL. Denervation dramatically accelerated the initial and the maximal rates of the transport in EDL, whereas it significantly reduced those in SL. In contrast, the electrical stimulation of sciatic nerve accelerated the uptake of taurine by EDL and SL of the control but not of the curare-treated rats. These results suggest that transport of taurine into rat skeletal muscles is regulated differently by neural information and by muscular activity, and that the regulation is dependent on the muscle phenotype.