Evaluation of disuse atrophy of rat skeletal muscle based on muscle energy metabolism assessed by 31P-MRS

The purpose of this study was to evaluate disuse atrophy of skeletal muscle using a hind-limb suspension model, with special reference to energy metabolism. Twenty-four Sprague-Dawley rats were divided into four groups: control group (C), hind-limb suspended for 3 days (HS-3), for 7 days (HS-7) and for 14 days (HS-14). The gastrocnemius-plantaris-soleus (GPS) muscles in each group were subjected to the following measurements. After a 2-min rest, contraction of the GPS muscles was induced by electrical stimulation of the sciatic nerve at 0.25 Hz for 10 min, then the frequency was increased to 0.5 and 1.0 Hz every 10 min. During the stimulation, twitch forces were recorded by a strain gauge, and 31P-MRS was performed simultaneously. Maximum tension was measured at the muscle contraction induced at 0.25 Hz; the wet weight of the whole and each muscle in the GPS muscles was also measured. From the 31P-MR spectra during muscle contraction, the oxidative capacity was calculated and compared among the groups. The weights of the whole GPS muscles in C, HS-3, HS-7 and HS-14, were 2.66 +/- 0.09, 2.39 +/- 0.21, 2.34 +/- 0.21 and 2.18 +/- 0.14 (g) respectively. Thus, the muscle mass significantly decreased with time (p < 0.05). Among the GPS muscles, the decrease in weight of the soleus muscle was especially remarkable; in the HS-14 group its weight decreased to 60% of that in the C group. We evaluated maximum tension and oxidative capacity as the muscle function. The maximum tensions in C, HS-3, HS-7 and HS-14 were 519 +/- 43, 446 +/- 66, 450 +/- 23 and 465 +/- 29 (g), respectively. This was significantly greater in the C group than in any other groups, however there were no significant differences among the three HS groups. The oxidative capacity during muscle contraction in the C group was higher than in any HS group and it did not further decrease even if the suspension of the limbs was prolonged beyond 3 days. The present study showed that in disuse atrophy, muscle mass and muscle function did not change simultaneously. Thus, it is necessary to develop countermeasures to prevent muscle atrophy and muscle function deterioration independently.     

Staircase potentiation in isolated frog skeletal muscle: power spectral analysis of the evoked compound muscle action potential

1. The mechanical and electrophysiological effects of repetitive, low-frequency electrical stimulation on paired sartorii muscles from small male frogs have been investigated, in vitro. 2. Stimulation for 90 sec at 5 Hz resulted in a progressive rise (staircase) than fall (fatigue) in peak twitch tension. 3. The root mean square amplitude, peak-to-peak amplitude, conduction velocity and mean power frequency of evoked compound muscle action potentials (CMAPs) decreased over the stimulation period. 4. Results suggest that alterations in the shape of the CMAP during repetitive stimulation may contribute to the staircase phenomenon.     

A comparison of the contractile properties of the human gastrocnemius and soleus muscles

Twitch speeds and potentiating capacities have been determined for human medial and lateral gastrocnemius and soleus muscles. The experiments involved and application of submaximal stimuli to the respective muscle bellies, with monitoring of the evoked compound action potentials (M-waves) during repetitive stimulation. Contrary to an earlier report, the lateral gastrocnemius was found to have a significantly shorter mean contraction time (100.0 +/- 10.8 ms) than the soleus (156.5 +/- 14.7 ms) and this value was also significantly different from that of the medial gastrocnemius (113.7 +/- 19.6 ms). The mean half-relaxation time for each muscle also differed significantly from those for the other two muscles. A further contrast between the muscles was that potentiation of the twitch, following a 3-s tetanus at 50 Hz, was significantly greater in the lateral gastrocnemius than in soleus (mean values 60.4 +/- 43.1% and 2.6 +/- 3.3% respectively.     

Hindlimb muscular contraction reflexly decreases total pulmonary resistance in dogs

We have previously shown that contraction of the gracilis muscles of anesthetized dogs reflexly relaxes tracheal smooth muscle. We have also found that electrical stimulation of these afferents decreases total pulmonary resistance (TPR), a calculation that provides a functional index of airway caliber. Despite these findings, we have yet to show that muscular contraction reflexly decreases TPR. Therefore, in 11 alpha-chloralose-anesthetized dogs, we contracted the hindlimb muscles by electrically stimulating the L6-L7 ventral roots while measuring TPR breath by breath. We found that static contraction decreased TPR from 12.6 +/- 1.1 to 10.4 +/- 0.9 cmH2O X l-1 X s (P less than 0.05). This decrease was reflex in origin because it was prevented by section of the spinal roots innervating the working hindlimb. Repetitive twitch contractions (5 Hz) also reflexly decreased TPR, but the effect was smaller than that evoked by static contraction. The reflex decreases in TPR evoked by contraction were unaffected by propranolol but were abolished by atropine. We conclude that muscular contraction dilates the airways by a reflex mechanism whose efferent arm consists of a withdrawal of cholinergic input to airway smooth muscle.     

Force-frequency relationship and potentiation in mammalian skeletal muscle.

Repetitive activation of a skeletal muscle results in potentiation of the twitch contractile response. Incompletely fused tetanic contractions similar to those evoked by voluntary activation may also be potentiated by prior activity. We aimed to investigate the role of stimulation frequency on the enhancement of unfused isometric contractions in rat medial gastrocnemius muscles in situ. Muscles set at optimal length were stimulated via the sciatic nerve with 50-micros duration supramaximal pulses. Trials consisted of 8 s of repetitive trains [5 pulses (quintuplets) 2 times per second or 2 pulses (doublets) 5 times per second] at 20, 40, 50, 60, 70, and 80 Hz. These stimulation frequencies represent a range over which voluntary activation would be expected to occur. When the frequency of stimulation was 20, 50, or 70 Hz, the peak active force (highest tension during a contraction - rest tension) of doublet contractions increased from 2.2 +/- 0.2, 4.1 +/- 0.4, and 4.3 +/- 0.5 to 3.1 +/- 0.3, 5.6 +/- 0.4, and 6.1 +/- 0.7 N, respectively. Corresponding measurements for quintuplet contractions increased from 2.2 +/- 0.2, 6.1 +/- 0.5, and 8.7 +/- 0.7 to 3.2 +/- 0.3, 7.3 +/- 0.6, and 9.0 +/- 0.7 N, respectively. Initial peak active force values were 27 +/- 1 and 61.5 +/- 5% of the maximal (tetanic) force for doublet and quintuplet contractions, respectively, at 80 Hz. With doublets, peak active force increased at all stimulation frequencies. With quintuplets, peak active force increased significantly for frequencies up to 60 Hz. Twitch enhancement at the end of the 8 s of repetitive stimulation was the same regardless of the pattern of stimulation during the 8 s, and twitch peak active force returned to prestimulation values by 5 min. These experiments confirm that activity-dependent potentiation is evident during repeated, incompletely fused tetanic contractions over a broad range of frequencies. This observation suggests that, during voluntary motor unit recruitment, derecruitment or decreased firing frequency would be necessary to achieve a fixed (submaximal) target force during repeated isometric contractions over this time period.     

Posttetanic potentiation and skeletal muscle fatigue: interactions with caffeine

The purpose of this study was to determine the interaction of three factors that modify twitch contraction amplitude in the rat gastrocnemius muscle in situ: posttetanic potentiation, fatigue, and caffeine. Posttetanic (200 Hz for 1 s) twitch responses were observed before and after 15 Hz stimulation for 6 min (group FS), injection of caffeine (75 mg/kg dissolved in saline, group NC), a combination of both repetitive stimulation and caffeine injection (group FC), or no treatment (group NS). Developed tension increased significantly with posttetanic potentiation and caffeine injection and these potentiating factors were additive (group NC). Repetitive stimulation attenuated the twitch response and the fatigued muscle was still responsive to the potentiating factors. Posttetanic potentiation was accomplished primarily by a significant increase in the peak rate of force development whereas caffeine potentiation and fatigue were effected with a proportional change in contraction time. It seems likely that the mechanism of posttetanic potentiation is not the same as the mechanism of caffeine-induced potentiation. Caffeine-induced potentiation is known to be related to increased release of calcium. Because changes in contraction time with fatigue were opposite to those associated with caffeine potentiation, it is proposed that the attenuated twitch response in fatigue results from reduced release of calcium.     

TTX-induced muscle disuse alters Ca2+ activation characteristics of myofibril ATPase.

1. Previous reports of the effects of disuse induced by tetrodotoxin (TTX) have demonstrated alterations in muscle function suggesting changes in the quality of contractile proteins. 2. We extended these studies to the effects of TTX-induced disuse on the Ca2+ activation characteristics of myofibrillar ATPase of the rat gastrocnemius. 3. Atrophic responses were as previously reported (St-Pierre, D.M.M. and Gardiner P.F. (1985) Effect of disuse on mammalian fast-twitch muscle: joint fixation compared with neurally applied tetrodotoxin. Exp. Neurol. 90, 635-651; St-Pierre, D.M.M. et al. (1987). Recovery of muscle from tetrodotoxin-induced disuse and the influence of daily exercise; 1. Contractile properties. Exp. Neurol. 98, 472-488.) with a significant decrease in left gastrocnemius weight compared to control (C) (1.25 +/- 0.06 for C vs 0.72 +/- 0.04 for TTX, X +/- SEM, P less than or equal to 0.01). 4. Myofibrillar protein yield (mg/g wet weight) was also depressed (92.8 +/- 4.5 for C vs 70.3 +/- 3.7 for TTX; P less than or equal to 0.01). 5. Maximum ATPase of myofibrils (nmol Pi/mg/min) was decreased (441 +/- 28 for C vs 181 +/- 30 for TTX, P less than or equal to 0.01). 6. Furthermore, the Hill n which reflects the cooperative aspects of Ca2+ activation of the myofibrillar ATPase was depressed (1.58 +/- 0.07 for C vs 1.29 +/- 0.09 for TTX; P less than or equal to 0.01). 7. The results suggest that muscle perturbations resulting from disuse are partially related to changes in the myofibril.     

Diaphragmatic fatigue in the rat

We studied fatigue of rat diaphragm in response to repetitive brief and prolonged electrical stimulation of the phrenic nerve, at 0.2, 1-100 Hz. Low and high frequency of stimulation produced twitch and tetanic contractions in the rat diaphragm. A mean maximum twitch tension of 1.4 +/- 0.1 g was produced at 1 Hz, and a mean maximum tetanic tension of 5.6 +/- 0.3 g was obtained at 100 Hz (means +/- S.E., n = 8). Twitch and tetanic fatigue was produced at all frequencies of stimulations, but with different time scale, or duration, and with different number of stimuli delivered to the muscle. At low rates of stimulation, e.g. 10 Hz, fewer stimuli were needed to fatigue the muscle (3000 in 5 min), whereas at high rates of stimulation, e.g. 50 Hz, more stimuli were needed to fatigue the muscle (6600 in 2.2 min). The amplitude of the tetanic tensions elicited at 10 and 50 Hz, at the end of 5 or 2 min fatiguing stimulation, was 39 +/- 2.7% and 80 +/- 3.1% of their respective control tensions (2.8 +/- 0 2 g and 5.3 +/- 0.5 g, n = 8, P 0.001). It was concluded that fatigue in the rat diaphragm depended on the frequency and duration of stimulation as well as on the number of stimuli delivered to the muscle. Various mechanisms of muscle fatigue are described in the discussion to explain the observations made in the present investigation.     

Contractile and endurance properties of geniohyoid and diaphragm muscles

Despite the wealth of information about the neural control of pharyngeal dilator muscles, little is known about their intrinsic physiological properties. In the present study the in situ isometric contractility and endurance of a pharyngeal dilator, the geniohyoid muscle, were compared with properties of the diaphragm in 12 anesthetized artificially ventilated cats. The contraction time (means +/- SE) of the geniohyoid (27 +/- 2 ms) was shorter than that of the diaphragm (36 +/- 3 ms; P less than 0.0005), as was the half-relaxation time (29 +/- 2 vs. 45 +/- 4 ms; P less than 0.002). The faster contraction and relaxation of the geniohyoid compared with the diaphragm were appropriately reflected in the shape of the force-frequency curves for the two muscles, with that of the geniohyoid located to the right of the diaphragm force-frequency curve. The endurance properties of the two muscles were assessed using repetitive stimulation at 40 Hz in trains lasting 0.33 s, with one train repeated every second. The ratio of force at the end of 2 min of repetitive stimulation to initial force was 0.67 +/- 0.06 for the geniohyoid and 0.15 +/- 0.03 for the diaphragm (P less than 0.00001). After the repetitive stimulation, the muscle force generated in response to a range of stimulus frequencies was reduced to a greater extent for the diaphragm than for the geniohyoid muscle. These results indicate that the geniohyoid muscle has a faster physiological profile than does the diaphragm yet is relatively resistant to fatigue when driven at high rates.     

Muscle contractility in chronic disorders of neuromuscular transmission

Muscle contractility of the thumb was studied in 24 normal subjects, 84 patients with myasthenia and 4 patients with hypothyrosis in response to supramaximal stimulation, on the basis of the time of contraction and semi-relaxation, staircase phenomena, and posttetanic potentiation. During hormonal therapy, the patients with myasthenia and those with hypothyrosis treated by substitution therapy manifested the normalization of the staircase and posttetanic potentiation, reduction of the contraction force and twitch time during single contraction. The comparison of the changes seen in the contraction force, staircase and posttetanic potentiation during examination of the patients over time suggested that the muscle has a regulatory system that determines the force and twitch time of muscle contraction.     

甲状腺功能亢进大鼠比目鱼肌肌浆网Ca2+-ATP酶活性增高可加速强直收缩疲劳

甲状腺功能亢进(甲亢)时甲状腺素分泌增加,不仅使具有神经支配的慢缩型肌纤维向快缩型转化,而且改变骨骼肌的强直收缩功能.因此,甲亢性肌病的肌肉乏力可能与骨骼肌强直收缩易发生疲劳有关.本实验在离体条件下,观测甲亢4周引起的大鼠慢缩肌--比目鱼肌(soleus, SOL)单收缩与间断强直收缩功能的变化.结果显示,甲亢4周大鼠体重明显低于同步对照组[(292±13)g vs (354±10)g],但SOL湿重没有明显改变[(107.3±8.6)mg vs (115.1±6.9)mg].甲亢大鼠SOL单收缩张力达到峰值的时间(time to peak tension, TPT)、从峰值降至75%舒张时间(time from peak tension to 75% relaxation, TR75)均明显缩短;强直收缩的TR75也明显缩短[(102.8±4.1)ms vs (178.8±15.8)ms];强直收缩的最适频率从对照组的100Hz增加到140Hz;间断强直收缩期间容易发生疲劳.甲亢大鼠SOL肌浆网Ca2 -ATP酶(sarcoplasmic-reticulum Ca2 -ATPase, SERCA)活性增高.采用SERCA特异性抑制剂CPA (1.0μmol/L)处理后,对照组与甲亢大鼠SOL间断强直收缩的TR75均延长,同时不易出现疲劳.5.0μmol/L CPA灌流虽可进一步抵抗甲亢大鼠SOL间断强直收缩引起的疲劳,但强直收缩期间的静息张力却明显升高.将CPA浓度增至10.0μmol/L,甲亢大鼠SOL间断强直收缩又趋向易发生疲劳.这些结果提示,与心肌相同,骨骼肌肌纤维SERCA活性亦可影响单收缩与强直收缩的舒张时间,SERCA活性升高可加速间断强直收缩发生疲劳.     

Reports of the length dependence of fatigue are greatly exaggerated.

Relative force depression associated with muscle fatigue is reported to be greater when assessed at short vs. long muscle lengths. This appears to be due to a rightward shift in the force-length relationship. This rightward shift may be caused by stretch of in-series structures, making sarcomere lengths shorter at any given muscle length. Submaximal force-length relationships (twitch, double pulse, 50 Hz) were evaluated before and after repetitive contractions (50 Hz, 300 ms, 1/s) in an in situ preparation of the rat medial gastrocnemius muscle. In some experiments, fascicle lengths were measured with sonomicrometry. Before repetitive stimulation, fascicle lengths were 11.3 +/- 0.8, 12.8 +/- 0.9, and 14.4 +/- 1.2 mm at lengths corresponding to -3.6, 0, and 3.6 mm where 0 is a reference length that corresponds with maximal active force for double-pulse stimulation. After repetitive stimulation, there was no change in fascicle lengths; these lengths were 11.4 +/- 0.8, 12.6 +/- 0.9, and 14.2 +/- 1.2 mm. The length dependence of fatigue was, therefore, not due to a stretch of in-series structures. Interestingly, the rightward shift that was evident when active force was calculated in the traditional way (subtraction of the passive force measured before contraction) was not seen when active force was calculated by subtracting the passive force that was associated with the fascicle length reached at the peak of the contraction. This calculation is based on the assumption that passive force decreases as the fascicles shorten during a fixed-end contraction. This alternative calculation revealed similar postfatigue absolute active force depression at all lengths. In relative terms, a length dependence of fatigue was still evident, but this was greatly diminished compared with that observed when active force was calculated with the traditional method.     

Changes in contractile properties and neuromuscular propagation evaluated by simultaneous mechanomyogram and electromyogram during experimentally induced hypothermia.

The present study examined, whether or not mechanomyogram (MMG) amplitude and frequency component could reflect the contractile properties of the triceps surae muscles, composed of relatively slow soleus (SOL) and fast medial gastrocnemius (MG), during experimentally induced hypothermia condition. In eight male subjects, lying in prone position, supramaximal single twitch and repetitive electrical stimulations at 10 Hz were applied at the intramuscular temperatures of control (34 degrees C), 15, 20, and 25 degrees C, respectively. The hypothermia induced substantial reduction in muscle contractile properties, e.g. prolonged twitch contraction and half relaxation times, resulted in a highly significant reduction in the fluctuation of force signal during the repetitive stimulations. These changes were almost mirrored by the similar and significant reductions in the MMG amplitude in both SOL and MG. Power spectrum analysis revealed that peak frequency components of MMG and fluctuation of force were almost matched with the applied stimulation frequencies, independent of the temperature condition. These results strongly suggest that MMG analysis could be employed to study muscle contractile properties varying across different physiological conditions.     

Optimal stimulation of paralyzed muscle after human spinal cord injury.

Muscle properties change profoundly as a result of disuse after spinal cord injury. To study the extent to which these changes can be reversed by electrical stimulation, tibialis anterior muscles in complete spinal cord-injured subjects were stimulated for progressively longer times (15 min, 45 min, 2 h, and 8 h/day) in 6-wk intervals. An index of muscle endurance to repetitive stimulation doubled (from 0.4 to 0.8), contraction and half-relaxation times increased markedly (from 70 to approximately 100 ms), but little or no change was measured in twitch or tetanic tension with increasing amounts of stimulation. The changes observed with 2 h/day of stimulation brought the physiological values close to those for normal (control) subjects. A decrease in the stimulation period produced a reversal of the changes. No effects were observed in the contralateral (unstimulated) muscle at any time, nor was there evidence of decreased numbers of motor units in these subjects secondary to spinal cord injury. Motor unit properties changed in parallel with those of the whole muscle. The occasional spasms occurring in these subjects are not sufficient to maintain normal muscle properties, but these properties can largely be restored by 1-2 h/day of electrical stimulation.     

Sarcolipin overexpression in rat slow twitch muscle inhibits sarcoplasmic reticulum Ca2+ uptake and impairs contractile function

Sarcolipin (SLN) is an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs) in vitro, but its function in vivo has not been defined. NF-SLN cDNA (SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus muscle in one hindlimb by plasmid injection and electrotransfer. Western blotting showed expression and co-immunoprecipitation showed physical interaction between NF-SLN and SERCA2a. Contractile properties and SERCA2a function were assessed and compared with vector-injected contralateral soleus muscles. NF-SLN reduced both peak twitch force (P(t)) (123.9 +/- 12.5 versus 69.8 +/- 8.9 millinewtons) and tetanic force (P(o)) (562.3 +/- 51.0 versus 300.7 +/- 56.9 millinewtons) and reduced both twitch and tetanic rates of contraction (+dF/dt) and relaxation (-dF/dt) significantly. Repetitive stimulation (750-ms trains at 50 Hz once every 2 s for 3 min) showed that NF-SLN increased susceptibility to fatigue. These changes in contractile function were observed in the absence of endogenous phospholamban, and NF-SLN had no effect on either SERCA2a or SERCA1a expression levels. NF-SLN also decreased maximal Ca(2+) transport activity at pCa 5 by 31% with no significant change in apparent Ca(2+) affinity (6.36 +/- 0.07 versus 6.39 +/- 0.08 pCa units). These results show that NF-SLN expression impairs muscle contractile function by inhibiting SERCA function and diminishing sarcoplasmic reticulum Ca(2+) stores.     

K+-induced twitch potentiation is not due to longer action potential

The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.     

Nerve stimulation decreases malonyl-CoA in skeletal muscle.

This study was designed to determine the effect of in situ electrical stimulation of the sciatic nerve on malonyl-CoA, an inhibitor of carnitine palmitoyl transferase, in the gastrocnemius/plantaris muscle group of rats. The left sciatic nerve was stimulated at a frequency of 5 Hz with 100-ms trains of impulses (50 Hz) for 1, 3, or 5 min. At the end of stimulation, the left and right (nonstimulated) gastrocnemius/plantaris muscle groups were clamp-frozen and later analyzed for malonyl-CoA and other metabolites. No change was observed in the noncontracting contralateral muscles in malonyl-CoA, ATP, creatine phosphate (CP), or citrate. In the stimulated muscles, malonyl-CoA decreased from 1.7 +/- 0.1 to 1.0 +/- 0.1 nmol/g (P less than 0.05), and CP decreased from 15.8 +/- 0.9 to 12.2 +/- 1.0 mumol/g (P less than 0.05) after 3 min of stimulation. After 5 min of stimulation, malonyl-CoA was 1.0 +/- 0.1 nmol/g and CP was 10.3 +/- 1.3 mumol/g. When muscles were stimulated for 5 min with single impulses (5 Hz), malonyl-CoA was decreased from 1.8 +/- 0.3 to 1.0 +/- 0.1 nmol/g, with no change in CP, ATP, or adenosine 3',5'-cyclic monophosphate. Thus a decline in malonyl-CoA can be induced by muscle contraction independently of humoral influence.     

Tetrodotoxin blocks mechanical response in mammalian muscle in the presence of tetrodotoxin-resistant action potentials

The effect of tetrodotoxin (TTX) (10(-5)-10(-6)M) on the mechanical activity and on the action potential of innervated and denervated muscle of the rat was studied. The twitch tension was reduced to 10 % of the control values within 20 min of TTX 10(-6) introduction. This effect was reversible. The mean twitch tension in the presence of 10(-6)M TTX expressed as a percentage of control was 9.3 +/- 2.4 (SEM) for innervated muscle and 10.9 +/- 2.5 for denervated muscle. The dose-effect twitch relation for denervated muscles was not significantly different from that observed in control innervated muscles in the 10(-3)-10(-6) TTX range. Action potentials of innervated muscles could not be elicited in 10(-6)M TTX. In the presence of this (TTX) fibers of chronically denervated muscles consistently responded to stimulation with action potentials which were slower and smaller but still with overshoot, contrasting with fibrillation potentials that had been described to be blocked by TTX.     

Postactivation potentiation influences differently the nonlinear summation of contractions in young and elderly adults.

The force enhancement of a twitch after a maximal conditioning muscle contraction [i.e., postactivation potentiation (PAP)] is reduced with aging, but its influence on the summation of force in response to repetitive stimulation at different frequencies is not known. The purpose of this work was to compare the electrically evoked mechanical responses of the tibialis anterior muscle between young and elderly adults after a 6-s maximal voluntary contraction (MVC). The results showed that, immediately after the conditioning MVC, twitch torque and its maximal rate of development and relaxation were significantly enhanced in both groups, but the magnitude of potentiation was greater in young (148.0 +/- 14.2, 123.7 +/- 16.5, and 185.4 +/- 36.5%, respectively) compared with elderly adults (87.4 +/- 15.2, 63.8 +/- 9.9, and 62.9 +/- 11.0%, respectively). This age-related difference in potentiation of the twitch disappeared completely 1 min after the conditioning MVC. The potentiation of torque and speed-related parameters in response to two- and three-pulse trains, delivered at a constant interval of 10 ms (100 Hz), was less than for a single pulse for both groups. In young adults, the magnitude of PAP on the successive individual mechanical contributions within a train of stimuli declined progressively such that the third contribution did not differ significantly from the same contribution before the conditioning MVC. In contrast, the second and third contributions did not potentiate (P > 0.05) in elderly adults. Although these contributions did potentiate significantly at a lower frequency of stimulation (20 Hz) in the two groups, the difference in PAP between young and elderly adults still persisted. This overall attenuation of potentiation with aging, however, appears to have a moderate influence on the decrement of the muscular performance.     

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.