Impact of treadmill locomotor training on skeletal muscle IGF1 and myogenic regulatory factors in spinal cord injured rats

The objective of this study was to determine the impact of treadmill locomotor training on the expression of insulin-like growth factor I (IGF1) and changes in myogenic regulatory factors (MRFs) in rat soleus muscle following spinal cord injury (SCI). Moderate, midthoracic (T₈) contusion SCIs were produced using a NYU (New York University) impactor. Animals were randomly assigned to treadmill training or untrained groups. Rats in the training group were trained starting at 1 week after SCI, for either 3 bouts of 20 min over 1.5 days or 10 bouts over 5 days. Five days of treadmill training completely prevented the decrease in soleus fiber size resulting from SCI. In addition, treadmill training triggered increases in IGF1, MGF and IGFBP4 mRNA expression, and a concurrent reduction of IGFBP5 mRNA in skeletal muscle. Locomotor training also caused an increase in markers of muscle regeneration, including small muscle fibers expressing embryonic myosin and Pax7 positive nuclei and increased expression of the MRFs, myogenin and MyoD. We concluded that treadmill locomotor training ameliorated muscle atrophy in moderate contusion SCI rats. Training-induced muscle regeneration and fiber hypertrophy following SCI was associated with an increase in IGF1, an increase in Pax7 positive nuclei, and upregulation of MRFs.     

Changes in muscle T 2 relaxation properties following spinal cord injury and locomotor training

Magnetic resonance (MR) is frequently used to study structural and biochemical properties of skeletal muscle. Changes in proton transverse relaxation (T ₂) properties have been used to study muscle cellular damage, as well as muscle activation during exercise protocols. In this study, we implemented MR imaging to characterize the T ₂ relaxation properties of rat hindlimb muscles following spinal cord injury (SCI) and locomotor training. After moderate midthoracic contusion SCI, Sprague–Dawley rats were assigned to either treadmill training, cycle training or an untrained group. T ₂ weighted images were obtained and mean muscle T ₂ times were calculated in the tibialis anterior, soleus, and gastrocnemius (GAS) muscles at pre-injury as well as at 1, 2, 4, 8, and 12 weeks post-injury. Following SCI, hindlimb muscles in untrained animals showed a significant increase in muscle T ₂, with the most dramatic shift (+5.46 ms) observed in soleus muscle at 1 week post-SCI. Subsequently, all muscle groups showed a spontaneous recovery in muscle T ₂ with normalized T ₂ values in the GAS and tibilias anterior muscles at 4 weeks and the soleus at 12 weeks post-SCI. Both training paradigms, treadmill and cycling training, accelerated the recovery of soleus muscle T ₂. As a result, soleus muscle T ₂ recovered back to pre-injury values within 3 weeks of training in both training groups. Finally, in vitro histological assessments of rat skeletal muscles demonstrated that there was no apparent muscle injury in any of the muscles studied at 1 week post-SCI.     

Effects of streptozotocin-induced diabetes on leg muscle contractile properties and motor neuron morphology in rats

Skeletal muscle fiber subtypes are differentially sensitive to diabetes-related pathology; For example, fast-twitch muscles exhibit severe decreases in contraction force while slow-twitch muscles demonstrate prolonged half-relaxation time. However, such alterations have only been examined after a relatively short period following diabetes onset, with no information available regarding muscle damage caused by longer disease periods (>20 weeks). This study examined alterations in the contractile properties of the medial gastrocnemius (fast-twitch) and soleus (slow-twitch) muscles, as well as morphological changes in their motor neurons 12 and 22 weeks after diabetes onset. Adult male Wistar rats were divided into diabetic (12- or 22-week post-streptozotocin injection) and age-matched control groups. Electrically evoked maximum twitch and tetanic tension were recorded from leg muscles. Additionally, motor neuron number and cell body size were examined. At 12 weeks after diabetes onset, decreases in twitch force were observed predominantly in medial gastrocnemius muscles, while soleus muscles exhibited prolonged half-relaxation time. However, these differences became ambiguous at 22 weeks, with decreased twitch force and prolonged half-relaxation time observed in both muscles. On the other hand, reduction in soleus motor neurons was observed 12 weeks after diabetes onset, while medial gastrocnemius motor neurons were diminished at 22 weeks. These data indicate that experimental diabetes induces differential damage to medial gastrocnemius and soleus muscles as well as motor neurons. These diabetes-induced differences may partly underlie the differential deficits observed in gastrocnemius and soleus.     

Functional reorganization of soleus H-reflex modulation during stepping after robotic-assisted step training in people with complete and incomplete spinal cord injury

Body weight–supported (BWS) robotic-assisted step training on a motorized treadmill is utilized with the aim to improve walking ability in people after damage to the spinal cord. However, the potential for reorganization of the injured human spinal neuronal circuitry with this intervention is not known. The objectives of this study were to determine changes in the soleus H-reflex modulation pattern and activation profiles of leg muscles during stepping after BWS robotic-assisted step training in people with chronic spinal cord injury (SCI). Fourteen people who had chronic clinically complete, motor complete, and motor incomplete SCI received an average of 45 training sessions, 5 days per week, 1 h per day. The soleus H-reflex was evoked and recorded via conventional methods at similar BWS levels and treadmill speeds before and after training. After BWS robotic-assisted step training, the soleus H-reflex was depressed at late stance, stance-to-swing transition, and swing phase initiation, allowing a smooth transition from stance to swing. The soleus H-reflex remained depressed at early and mid-swing phases of the step cycle promoting a reciprocal activation of ankle flexors and extensors. The spinal reflex circuitry reorganization was, however, more complex, with the soleus H-reflex from the right leg being modulated either in a similar or in an opposite manner to that observed in the left leg at a given phase of the step cycle after training. Last, BWS robotic-assisted step training changed the amplitude and onset of muscle activity during stepping, decreased the step duration, and improved the gait speed. BWS robotic-assisted step training reorganized spinal locomotor neuronal networks promoting a functional amplitude modulation of the soleus H-reflex and thus step progression. These findings support that spinal neuronal networks of persons with clinically complete, motor complete, or motor incomplete SCI have the potential to undergo an endogenous-mediated reorganization, and improve spinal reflex function and walking function with BWS robotic-assisted step training.     

Activities of creatine kinase isoenzymes in single skeletal muscle fibres of trained and untrained rats

Biochemical changes in the creatine kinase isoenzyme compositions in single muscle fibres of different types in rats were induced by endurance running training. Single muscle fibres were dissected from the soleus and extensor digitorum longus muscles of Wistarstrain male rats trained on a motor-driven treadmill for 16 weeks. Each fibre was typed histochemically (SO, slow-twitch oxidative; FOG, fast-twitch oxidative glycolytic; FG, fast-twitch glycolytic), and the activities of total creatine kinase and its four isoenzymes (CK-MM, -MB,-BB, and mitochondrial creatine kinase) were measured. The endurance training did not affect the total creatine kinase activity, but resulted in significantly increased activities of CK-MB and CK-BB in SO and FOG fibres, and the mitochondrial enzyme activity in FOG and FG fibres. Endurance training induced biochemical changes in the isoenzyme compositions, specifically in FOG fibres. These results suggest that changes in creatine kinase isoenzymes with endurance training reflect changes in the energy metabolism in the different muscle fibres, supporting the hypothesis that the different isoenzymes play different roles in energy transduction.     

Different metabolic responses to exercise training programmes in single rat muscle fibres

Summary The aim of this report is to elucidate the effects of exercise training on metabolic properties of different muscle fibre types of the rat hindlimb. Single muscle fibres were dissected from soleus (SOL) or extensor digitorum longus (EDL) muscles of Wistar strain male rats trained on a treadmill for 16 weeks. Each fibre was typed histochemically (SO, slow-twitch oxidative; FOG, fast-twitch oxidative glycolytic; FG, fast-twitch glycolytic). Then glycolytic and oxidative enzymes (CK, LDH, PFK, PK, SDH, and MDH) activities were measured biochemically. Slow,-type fibres (SO) were hypertrophied following endurance training and fast-twitch fibres (FOG and FG) were hypertrophied following sprint training. In EDL muscles the distribution of the slow-type fibres was reduced following the sprint training. The activity of glycolytic enzymes increased significantly in the fast-type fibres (FOG and FG) following sprint training, while oxidative enzymes activities increased in both fast (FOG and FG) and slow (SO) muscle fibres following the endurance training. Neither glycolytic nor oxidative enzymes' activities always increased equally in all types of fibre following exercise training. Consequently, the metabolic profiles in each type of single muscle fibre were affected differently by different intensities of exercise training. These results suggest that the functional (enzymes activity) and structural (muscle fibre hypertrophy) changes of skeletal muscle fibre following exercise training appeared gradually, and would be controlled by different factors.     

Specific mitochondrial responses to running training are induced in each type of rat single muscle fibers

The effects of training by running (sprint or endurance) on the mitochondrial volume, number, and succinate dehydrogenase (SDH) activity of different types of single muscle fibers, and on the elemental composition of soleus and extensor digitorum longus muscles were studied employing histochemical, electron microscopic, and electron probe-micro analysis (EPMA). Newly weaned male Wistar rats were trained on a motor-driven treadmill endurance exercise for 14 weeks. The relative mitochondrial volume per single muscle fiber of slow-twitch oxidative (SO) fiber was significantly increased following endurance training (p less than 0.01). There was no significant correlation between mitochondrial volume and number of SO fibers following endurance exercise training. Following sprint training, both mitochondrial volume and number of fast-twitch oxidative glycolytic (FOG) fibers increased significantly (p less than 0.01), with significant correlation (r = 0.69) between these parameters. SDH activity was higher in the order of SO, FOG, and fast-twitch glycolytic (FG) fibers following endurance training; however, the activity was higher in the order FOG, SO, and FG fibers following sprint training. The potassium concentration in cytoplasm of the soleus muscle showed a tendency to decrease following both types of training. These results suggest that the oxidative capacity of each type of muscle fiber does not always increase equally following training. Changes in mitochondrial number and volume in response to the two different types of training differed according to the type of fiber.     

Phase shift in the REM sleep rhythm

Carbohydrate depletion during exercise was measured in the liver, in the three different types of skeletal muscle, and in the blood of exercise-trained and untrained rats. The acute exercise test consisted of 45 min of treadmill running of progressively increasing intensity. The training program consisted of 6 hrs of swimming per day, 5 days per week for 14 weeks; the training induced an increase of approximately 35 percent in the respiratory capacity of gastrocnemius muscle, and a 14 percent incrase in heart weight. Glycogen stores in fast-twitch red, fast-twitch white, and slow-twitch red types of skeletal muscle, were depleted significantly more slowly in the trained than in the untrained animals during the treadmill exercise test. Resting glycogen stores in the liver were higher and were depleted more slowly during exercise in the trained than the untrained animals. Blood lactate concentration was significantly lower in the trained than in the untrained rats at the end of the exercise test. These results provide evidence that endurance exercise training induces adaptation which protect against the depletion of glycogen from the liver and from the tree types of skeletal muscle during prolonged exercise.     

Adaptation of actomyosin ATPase in different types of muscle to endurance exercise.

Higher concentrations of actomyosin were found in the red portion of the vastus lateralis and in the white portion of the vastus lateralis muscle than in the soleus or heart in rats. A strenuous program of treadmill running lasting 18 wk or longer did not significantly affect the amount of actomyosin recovered from the different types of muscle. No changes in actomyosin ATPase occurred in fast-twitch white (white vastus) or heart muscles in response to the exercise training. In contrast, a decrease of approximately 20% occurred in the specific activity of actomyosin ATPase of fast-twitch red (red vastus) muscle (0.635 +/- 0.029 mumol Pi/min per milligram for sedentary vs. 0.529 +/- 0.021 mumol Pi/min per milligram for trained), while the actomyosin ATPase activity of slow-twitch red (soleus) muscle increased about 20% (0.209 +/- 0.033 vs. 0.257 +/- 0.031 mumol Pi/min per milligram). There was a close correlation (r = 0.99, P less than 0.001) between actomyosin ATPase activity and phosphofructokinase activity in the three types of skeletal muscles and in heart muscle of exercise-trained and untrained animals, providing further evidence in support of the concept that the glycogenolytic capacity of a muscle and its actomyosin ATPase activity are regulated in parallel.     

Intracellular β2-adrenergic receptor signaling specificity in mouse skeletal muscle in response to single-dose β2-agonist clenbuterol treatment and acute exercise

The aim of this study was to clarify the intracellular β₂-adrenergic receptor signaling specificity in mouse slow-twitch soleus and fast-twitch tibialis anterior (TA) muscles, resulting from single-dose β₂-agonist clenbuterol treatment and acute exercise. At 1, 4, and 24 h after single-dose treatment with clenbuterol or after acute running exercise, the soleus and TA muscles were isolated and subjected to analysis. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased after single-dose clenbuterol treatment and acute exercise in the soleus muscle but not in the TA muscle. Although there was no change in the phosphorylation of Akt after acute exercise in either muscle, phosphorylation of Akt in the soleus muscle increased after single-dose clenbuterol treatment, whereas that in the TA muscle remained unchanged. These results suggest that p38 MAPK and Akt pathways play a functional role in the adaptation to clenbuterol treatment and exercise, particularly in slow-twitch muscles.     

Response of mitochondria of different types of skeletal muscle to thyrotoxicosis.

To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria.     

Effect of hypobaric hypoxia on rat soleus muscle fibers and their innervating motoneurons: a review

Mammalian skeletal muscle fibers are classified into three basic types based on their enzyme histochemical profiles: fast-twitch glycolytic (FG), fast-twitch oxidative glycolytic (FOG), and slow-twitch oxidative (SO) types. The type-shift of fibers from FOG to SO in the slow soleus muscle of rats occurs during postnatal growth. Our previous studies have demonstrated that hypoxic exposure inhibits a growth-related type-shift of fibers from FOG to SO in the rat soleus muscle, irrespective of the duration and age at which the animals are exposed to hypoxia. Our previous studies have also revealed that a high percentage of FOG fibers in the soleus muscle of the hypoxia-adapted rats is found only under hypoxic conditions. Furthermore, we have found that these adaptations in fibers of the rat soleus muscle correspond well with those in motoneurons at the ventral horn of the spinal cord that innervate the muscle fibers.     

肿瘤坏死因子受体相关因子6在大鼠失神经支配后胫前肌与比目鱼肌中的表达变化

目的 通过蛋白质组学方法分析失神经支配后胫前肌与比目鱼肌的蛋白表达变化,探讨肿瘤坏死因子受体相关因子6（TRAF6）在失神经支配后胫前肌与比目鱼肌中的表达变化及其意义。 方法 制备大鼠坐骨神经离断模型,通过同位素相对标记与绝对定量 (iTRAQ)技术方法分析胫前肌与比目鱼肌在失神经支配后的蛋白表达变化,比较差异表达的蛋白在胫前肌与比目鱼肌中的差异,筛选出在胫前肌与比目鱼肌中的表达变化差异显著的关键蛋白,并通过免疫印迹法验证其表达,进一步通过体外方法验证关键蛋白的生物学作用。 结果 失神经支配后比目鱼肌萎缩速度和程度明显大于胫前肌（P<0.05,n=20）,蛋白质组学研究发现有30个蛋白在胫前肌与比目鱼肌中表达变化差异较为明显,这些蛋白主要包括代谢相关蛋白、伴侣蛋白、收缩蛋白以及信号分子等,其中TRAF6在失神经支配后比目鱼肌中表达显著上升,蛋白免疫印迹法检测结果也证实了蛋白质组学的结果,TRAF6的靶基因肌肉环状指蛋白1（MuRF1）和肌肉萎缩盒F基因（MAFbx)在失神经支配后比目鱼肌中的表达也高于其在胫前肌中的表达（P<0.05,n=6）;为了进一步探讨TRAF6对肌萎缩的影响,在肌管中转染TRAF6 siRNA和对照siRNA,然后用地塞米松诱导C2C12肌管萎缩,发现TRAF6 siRNA转染组肌管的直径明显大于转染对照siRNA组（P<0.05,n=6）;TRAF6、MuRF1和MAFBx在TRAF6 siRNA转染组肌管中的表达显著低于转染对照siRNA组（P<0.05,n=6）,结果提示TRAF6 siRNA有效抑制了靶基因TRAF6的表达,也同时抑制了其下游靶基因MuRF1和MAFBx的表达。 结论 TRAF6在失神经支配后比目鱼肌中的表达量显著高于其在胫前肌中的表达,抑制TRAF6的表达可以减轻地塞米松引起的肌管萎缩,由此推测失神经支配后比目鱼肌萎缩较胫前肌严重可能与失神经支配后比目鱼肌中TRAF6的升高更显著有关。     

Contractile properties, fatiguability and glycolytic metabolism in fast- and slow-twitch rat skeletal muscles of various temperatures

The influence of muscle temperature (28 and 36 degrees C) on fatiguability and glycolytic metabolism was studied during 5 min of intermittent stimulation of motor nerves of the tibialis anterior, extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles in the rat at 100 Hz (200 ms per s). The decline in isometric tension was not affected by muscle temperature either in fast- or in slow-twitch muscles. In fast-twitch muscles the utilization of glycogen during stimulation was the same at 28 and 36 degrees C, while in the soleus muscle it was lower at 28 degrees C. The concentration of glucose-6-phosphate immediately after stimulation was higher in the muscles at 28 degrees C than in those at 36 degrees C, whereas no difference in lactate concentration was found between the two temperature groups. These observations indicate that compared with the rate at 36 degrees C, the rate of glycogenolysis at 28 degrees C is unchanged in fast-twitch, but decreased in slow-twitch muscle. This might imply increased economy of ATP turnover during contraction in the soleus muscle at 28 degrees C.     

Effect of exercise on lipoprotein lipase activity in rat heart and skeletal muscle.

Lipoprotein lipase activity was measured in the three skeletal muscle fiber types of untrained rats and in those of rats subjected to a 12-wk program of treadmill running. Lipoprotein lipase activity in slow-twitch red fibers was approximately 14- to 20-fold higher (P less than 0.001) than that in fast-twitch white and approximately 2-fold higher (P less than 0.001) than that in fast-twitch red fibers in the untrained animals. These results suggest that, in sedentary animals, mainly slow-twitch red and fast-twitch red fibers are capable of taking up plasma triglyceride fatty acids. Regularly performed endurance exercise resulted in significant increase (2- to 4.5-fold) in lipoprotein lipase activity in the three muscle fiber types examined. The increase in lipoprotein lipase activity in response to treadmill running suggests that exercise increases the capacity of these fibers to take up and oxidize plasma triglyceride fatty acids. Cardiac muscle did not undergo an exercise-induced increase in the levels of activity of lipoprotein lipase similar to that seen in skeletal muscle.     

Calmitine: a calcium-binding mitochondrial protein specific for fast-twitch muscle fibers

Mitochondrial fractions were isolated from fast-twitch (EDL), slow-twitch (soleus) and heart muscle of normal rat (WKY). Protein separation by electrophoresis and study of calcium-45 binding showed that a specific calcium protein (designated as calmitine) was present in the mitochondria of fast-twitch muscle but practically inexistent in slow-twitch and cardiac muscle. It seems to be related to calcium uptake by an energy-dependent mechanism.     

Spatial distribution of motor unit fibres in fast- and slow-twitch rat muscles with special reference to age.

The spatial arrangement and morphometrical properties of the muscle fibres within single motor units (motor unit fibres) were studied in fast-twitch units of the tibialis anterior (TA) and in slow-twitch units of the soleus, using a computer-assisted model. The motor unit fibres were identified by the glycogen-depletion technique and the position of each fibre was defined by (x, y)-coordinates. The distance between each fibre and the nearest motor unit fibre (nearest-neighbour distance), and the distance between each fibre and each of the other fibres in the unit (interfibre distance), was calculated and plotted. Comparisons were made between young adult (3-6 months) and old (20-25 months) rats. In old animals, the motor units of TA and the soleus were larger (P less than 0.05 and P less than 0.01), contained an increased number of muscle fibres (P less than 0.01) and covered a larger portion of the muscle cross-section (P less than 0.01 and P less than 0.1). These changes indicate the presence of an age-related denervation-reinnervation process in both types of muscles. In the young adult group, the fast-twitch motor unit fibres of TA were non-randomly arranged (P less than 0.05-0.01) whereas the fibre arrangement within the slow-twitch motor units of the soleus was not significantly different from random. In old animals, the fibre arrangement was non-random in both fast- and slow-twitch motor units. In TA, the distribution of nearest-neighbour distances showed an increased (P less than 0.05) proportion of short distances in old age, whereas the distribution of interfibre distances was unchanged. In the soleus, the distribution of interfibre distances showed an age-related displacement to the left at short distances (P less than 0.05) and to the right at long distances (P less than 0.01), but the distribution of nearest-neighbour distances was not significantly altered. It is concluded that motor unit fibres are non-randomly arranged in the fast-twitch motor units studied and that a non-random rearrangement of motor unit fibres takes place in both fast- and slow-twitch units during the ageing process. This age-related rearrangement is secondary to a denervation-reinnervation process and it appears as if different types of reinnervation predominate in fast- and slow-twitch units.     

Differential gene expression of muscle-specific ubiquitin ligase MAFbx/Atrogin-1 and MuRF1 in response to immobilization-induced atrophy of slow-twitch and fast-twitch muscles

We examined muscle-specific ubiquitin ligases MAFbx/Atrogin-1 and MuRF1 gene expression resulting from immobilization-induced skeletal muscle atrophy of slow-twitch soleus and fast-twitch plantaris muscles. Male C57BL/6 mice were subjected to hindlimb immobilization, which induced similar percentage decreases in muscle mass in the soleus and plantaris muscles. Expression of MAFbx/Atrogin-1 and MuRF1 was significantly greater in the plantaris muscle than in the soleus muscle during the early stage of atrophy. After a 3-day period of atrophy, total FOXO3a protein level had increased in both muscles, while phosphorylated FOXO3a protein had decreased in the plantaris muscle, but not in the soleus muscle. PGC-1α protein expression did not change following immobilization in both muscles, but basal PGC-1α protein in the soleus was markedly higher than that in plantaris muscles. These data suggest that although soleus and plantaris muscles atrophied to a similar extent and that muscle-specific ubiquitin protein ligases (E3) may contribute more to the atrophy of fast-twitch muscle than to that of slow-twitch muscle during immobilization.     

Regulation of dihydropyridine receptor levels in skeletal and cardiac muscle by exercise training

To examine the influence of exercise training on the expression of dihydropyridine (DHP)-sensitive Ca²⁺ channels in skeletal and cardiac muscle, we have determined DHP receptor levels by [³H]PN200-110-binding and immunoblot analysis in homogenates and microsomal fractions of slow- and fast-twitch muscles and heart from rats subjected to a 12-week programme of moderate endurance training. We found that exercise increases the amount of DHP receptor in homogenates of the slow-twitch soleus (42%) and the fast-twitch extensor digitorum longus (60%). Comparable increases in DHP receptor density with training were also observed in the microsomal fractions isolated from both skeletal muscles; these increases were not due to differences in the membrane composition of the microsomal fractions, since the relative proportion of specific enzyme markers was not affected by exercise training. Levels of DHP receptor were not modified in cardiac muscle as a result of the exercise programme. These data suggest an up-regulation of the DHP receptor in the skeletal muscle as a consequence of exercise training, which may play a role in the adaptation of skeletal muscle to increased contractile activity.     

Muscle atrophy and histopathology of the soleus in 6-mercaptopurine-treated rats

This study was conducted to examine the histochemical changes occurring due to neonatal 6-mercaptopurine (6-MP) treatment (2 mg/kg, sc, between 2 and 22 days after birth) in the slow-twitch muscle (soleus) of adult male and female rats. At 6 months of age, the control and the 6-MP-treated rats were evaluated for the sciatic nerve conduction to the soleus and for the soleus atrophy and histopathology of the type I (slow-twitch) and type II (fast-twitch) muscle fibers. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in fiber areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.