Isometric Twitch Tension Research Articles

<b>EFFECT OE DENERVATION ON CONTRACTILE PROPERTIES AND MYOSIN LIGHT CHAIN PHOSPHORYLATION IN RAT PAST-TWITCH SKELETAL </b><b>MUSCLES </b>

Changes in the contractile properties and phosphorylation of myosin light chain 2 (LC2) in extensor digitorum longus (EDL) muscles of rats were studied for the 7-day period following denervation. Post-tetanic potentiation (PTP) of isometric twitch tension, a property of fast-twitch muscles, was recorded 10 sec after a 1-sectetanic stimulation (200 Hz) and the extent of LC2 phosphorylation was determined by urea-glycerol-acrylamide gel electrophoresis. The degree of PTP decreased and was almost abolished by 7 days after denervation. On the other hand, the extent of LC2 phosphorylation in the resting state decreased to about half of the control value after 1 day and fell to zero by 7 days. At 10 sec following the tetanic stimulation, the extent of LC2 phosphorylation of control muscles exceeded 50%, and this decreased to 32% after 1 day, and to 14% after 2 days. Virtually no phosphorylation reaction occurred after 3 days. The rates of reduction in PTP and LC2 phosphorylation following tetanic stimulation correlated well during the 7-day period after denervation. These results suggest that the innervation influences PTP in association with the regulation of LC2 phosphorylation, supporting the hypothesis that LC2 phosphorylation plays an important role in producing twitch tension potentiation in fast-twitch skeletal muscles.

Effects of an anabolic hormone on striated muscle growth and performance.

Chronic administration of an anabolic hormone, nandrolone phenylpropionate, in sedentary female rats for 6 weeks gave a 20% increase in body weight and the same proportional increase in all muscles sampled (heart, diaphragm, soleus, TA, EHP and EDL), such that the muscle/body weight ratio was unchanged. Cardiac muscle was unresponsive to treatment. Acute stimulation of EDL via lateral popliteal nerve gave similar values for contraction time, 1/2 relaxation time and twitch:tetanus ratio in both groups suggesting no slowing of the muscle. Fatigue resistance of EDL was improved with 0.29 +/- 0.029 vs. 0.46 +/- 0.071 of maximum isometric twitch tension being developed after 10 min repetitive stimulation at 4 Hz. This improved endurance was not accompanied by any increase in strength and could not be explained on the basis of cellular hypertrophy, but appears to reflect an increased aerobic capacity of skeletal muscle. The proportion of FOG fibres in EDL increased, 38 +/- 1.1% vs. 46 +/- 1.1%, and this was paralleled in the other skeletal muscles. Specific hypertrophy of FOG and FG fibres could be conclusively demonstrated in soleus and TA, respectively.

Structural and functional aspects of the actomyosin complex from fast-twitch muscle of euthyroid and hypothyroid rats

The effects of hypothyroidism on structural and functional properties of the actomyosin-ATPase complex of rat fast-twitch gastrocnemius muscle were examined and related to energetic and mechanical parameters. Hypothyroidism resulted in the appearance of a small band of the myosin heavy chain subunit of the slow form (MHCs) 8% of total MHC) which was absent in the euthyroid group. This observation corresponded with lower activities of myofibrillar ATPase (-14%) and Ca-activated myosin ATPase (-9%) in the hypothyroid group, although these changes were not significant. No effect of hypothyroidism on the Ca2+-sensitivity of the myofibrillar-ATPase activity was observed and tetanic force was not changed. Twitch force, however, was significantly increased by hypothyroidism. The degree of myosin P-light chain phosphorylation (percentage of total amount of P-light chain) determined after 5 and 10 s of tetanic stimulation (130 Hz, 35 degrees C), respectively, proved to be significantly lower in the hypothyroid group (5 s: 57%; 10 s: 61%) vs the euthyroid group (5 s: 79%; 10 s: 82%). There was no difference in P-light chain phosphorylation at rest between eu- and hypothyroids. The results suggest that a decreased actomyosin-ATPase activity can only in part contribute to the 30% lower energy turnover during force development found for fast-twitch skeletal muscle of hypothyroid rats. Moreover, the increase in twitch force by hypothyroidism cannot be explained by a change in myosin P-light chain phosphorylation. Isometric twitch tension potentiation after a 2 s tetanus and during low-frequency repetitive stimulation was reduced (up to -60%) in muscles of hypothyroid rats, which may well be related to the lower extent of P-light chain phosphorylation in hypothyroids.

Mechanical properties of rat skeletal muscle after hind limb suspension

It is clear that there are events which occur in response to neuromuscular activity that are essential to maintain normal muscle properties. Two factors thought to influence muscle contractile properties are tension and electrical activity. To study these variables the hind limbs of 10 postpubertal female Sprague-Dawley rats were prevented from supporting the weight of the body for 4 weeks, then in situ isometric properties were determined and compared with 10 age-matched control rats. The soleus (slow plantarflexor), the medial gastrocnemius (fast plantarflexor), and the tibialis anterior (fast dorsiflexor) were studied. The suspended soleus wet weight was 42% lower and the maximum isometric twitch ( P t) and tetanic ( P 0) tensions were 62 and 69% lower respectively, than in the control rats. The suspended medial gastrocnemius was 18% lower in wet weight and 14 and 9% lower in P 0 and P t than the controls. No differences in wet weight, P 0 or P t were observed in tibialis anterior. Mean contraction time was 22% shorter in the soleus, 9% in the medial gastrocnemius, and unchanged in the tibialis anterior following suspension. Further, the percent of P 0 attained during a 330-ms tetanus at 20 Hz was 15% lower in the suspended soleus and unchanged in the other two muscles. The fatigue index (ratio of tension after 2 min of stimulation at 40 Hz for 330 ms once per second to the maximum tension developed during the test) was unaffected by suspension in the soleus and tibialis anterior but was reduced from 49% to 36% in the medial gastrocnemius. The maximum rate of shortening of all three muscles was unaffected by suspension. These results indicate that suspension of the hind limbs selectively affects the mass and force-generating capabilities of the plantarflexors, particularly the predominantly slow soleus. In contrast, the fatigability of only the fast plantarflexor was increased whereas the slow plantarflexor was unaffected. These results, considered in light of collaborative studies, suggest that the chronic force-time levels in a muscle have an important influence on tension- and speed-related properties but not necessarily the fatigability of that muscle. Further, a marked difference in the sensitivity of the contractile elements of slow and fast muscle to this influence was evident.

Motor units in a skeletal muscle of neonatal rat: mechanical properties and weak neuromuscular transmission.

1. Isometric twitch and tetanic tensions were recorded from whole muscles and single motor units in isolated fourth deep lumbrical muscles from neonatal rats (most at 3-5 days old) and from older rats of various ages. 2. Whole-muscle time to peak contraction reduced from about 120 ms at birth to about 20-25 ms at 20 days and older. 3. The number of motor units in the muscle was constant with age (eleven on average) and there was no significant branching of motor axons below the common peroneal nerve branching point in the thigh. 4. In the 3-5 days age range, mean twitch:tetanus ratio for whole muscles was 0.299 and for single units was 0.177. As a consequence, mean motor unit size (as a percentage of whole-muscle tension) was greater for tetani (29.7%) than for twitches (19.9%). This was not the case in muscles from animals 22 days or older. Evidence is given that the cause of this is low junctional efficacy in some neuromuscular junctions in neonatal muscle. Intracellular recordings supported this view. 5. The relationships of motor-unit size to the contraction time, to the ratio of contraction time:half-relaxation time, and to fatigue index are given. There was no indication of clear segregation of motor units into more than one population, but it is concluded that small motor units are more likely to contain a higher proportion of slowly contracting, fatigue-resistant fibres than large units. 6. The level of overlap by axons in the lateral plantar nerve onto muscle fibres in a single sural nerve motor unit was greater in tetani than in twitches. The results indicate that the distribution of weak and strong inputs was not random, but that there was a tendency for one strong input to accompany a number of weak inputs (on average about two) on each muscle fibre. 7. Intracellular recording indicates that about 12% of fibres at 3-5 days may be electrically coupled.

Force, relaxation and energy metabolism of rat soleus muscle during anaerobic contraction.

Isolated soleus muscle of rat was stimulated electrically (2 Hz) for 7 min under anaerobic conditions. Isometric twitch tension decreased progressively and was 30% of the initial value at the end of stimulation. The decline in relative force was similar to that previously observed in fast twitch muscle and soleus can thus not be termed fatigue-resistant under anaerobic conditions. Phosphocreatine (PCr) decreased from (mean +/- SD) 61.1 +/- 4.4 at rest to 4.0 +/- 1.8 mmol kg-1 dry muscle (d.m.) after 7 min of stimulation, while lactate increased from 3.7 +/- 1.6 to 30 +/- 8 mmol kg-1 d.m. Energy was thus derived from complete utilization of PCr and a low rate of glycolysis resulting in an almost unchanged calculated intracellular pH. It is concluded that tension decline in soleus muscle is not due to decreased intracellular pH but is more related to the capacity to regenerate ATP at a sufficient rate. Contraction and relaxation time of the twitch remained practically constant during the stimulation period. In contrast prolonged activation of fast-twitch muscle results in a slowing of the relaxation of the twitch (Sahlin et al. 1981) and it has been suggested that this is caused by the decrease of intracellular pH. The constancy of both relaxation time and calculated pH in the fatigued soleus muscle is consistent with the hypothesis that there is a connection between these two parameters. In contrast to the twitch, relaxation of tension after a tetanus was prolonged in soleus. Hence, it appears that the rate limiting step for relaxation is different for a twitch than for a tetanus in soleus.

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on the contractile properties of reinnervated rat skeletal muscle

2,4-Dichlorophenoxyacetic acid (2,4-D), a common herbicide, was administered to rats (100 mg/kg, i.p.) during 24 days to determine whether or not it is toxic to regenerating peripheral nerve and reinnervating muscle. The peroneal nerve was crushed 1 cm proximal to the extensor digitorum longus muscle and recordings made in vivo after 1 to 24 days. Functional reinnervation was observed by day 10 and recovery was similar in rats receiving 2,4-D or vehicle. Distal motor latencies and muscle action potentials returned toward normal during the 24 days in a similar manner in 2,4-D and controls. Isometric twitch tensions per muscle weight on indirect stimulation returned to intact values by 17 days, but in the 2,4-D animals they became larger ( P < 0.01) than controls by day 24. The twitch:tetanus ratios were increased at day 10 and returned toward normal values in the controls but remained increased ( P < 0.01) in the 2,4-D animals at 24 days. Similar results were obtained on direct muscle stimulation. The data suggest that 2,4-D is not toxic to nerve during regeneration or muscle reinnervation in the rat, but that it does affect both twitch and tetanus tensions suggesting proliferation as well as disruption of myofibrils.

Phosphorylation of rabbit skeletal muscle myosin in situ.

Myosin light chain (P light chain) is phosphorylated by Ca2+ X calmodulin-dependent myosin light chain kinase. Based on studies with rat skeletal muscles, it has been shown that P light chain phosphorylation correlated to the extent of potentiation of isometric twitch tension. It is not clear whether this correlation exists in rabbit skeletal muscle, which has been the primary source of contractile proteins for biochemical studies. Therefore, phosphorylation of myosin P light chain in rabbit slow-twitch soleus and fast-twitch plantaris muscles in situ was examined. Electrical stimulation (5 Hz, 20 seconds) of plantaris muscle produced an increase in the phosphate content of P light chain from 0.17 to 0.45 mol phosphate/mol P light chain. This increase in phosphate content was accompanied by a 58% increase in maximal isometric twitch tension. Tetanic stimulation (100 Hz, 15 seconds) of rabbit soleus muscle resulted in only a small increase in P light chain phosphate content from 0.02 to 0.10 mol phosphate/mol P light chain, and posttetanic twitch tension did not increase significantly. The correlation between potentiated isometric twitch tension and P light chain phosphorylation in rabbit fast-twitch muscle is similar to that observed in rat skeletal muscle. These results were consistent with the hypothesis that phosphorylation of rabbit skeletal muscle myosin, which results in an increase in actin-activated ATPase activity, may be related to isometric twitch potentiation.

Regulation of myocardial contractility in exhaustive exercise

The impact of exhaustive exercise on myocardial function is poorly understood. Experimental parameters of contractility that are completely devoid of other influences do not exist. Furthermore, the problem is compounded by the fact that exhaustive work comprises myriad exercise paradigms and fatigue may be the result of numerous possible mechanisms. Despite these confounding variables, there is evidence that stroke volume may be impaired by prolonged work in humans. These studies implicated reduced venous return and not contractility as the reason. Experiments with the rat model have indicated that treadmill running at about 60% of VO2max results in reduced isometric twitch tension in isolated trabecular tissue. The data are consistent with the notion that contractility is substantially reduced. The mechanism for this inhibition is unknown. In separate studies using a similar model, it has been shown that Ca2+ uptake by the sarcoplasm reticulum of the myocardium in vitro is reduced by fatigue. It is conceivable that in exhaustive exercise, there may be only a slight effect on contractility in vivo but that substantial adjustments in intracellular homeostasis are required in order to achieve this. Future considerations should include a rigorous analysis of contractility and the factors that regulate it, as well as the choice of animal and exhaustion models.

Experimentally induced defects of mitochondrial metabolism in rat skeletal muscle. Biological effects of the mitochondrial uncoupling agent 2,4-dinitrophenol.

Infusion of dinitrophenol intra-arterially into rat hind limb caused an irreversible failure of isometric twitch tension and the induction of a severe progressive contracture. Metabolite analysis of muscle in which the twitch response had grossly fatigued revealed low levels of ATP and phosphocreatine together with lactate accumulation. Studies using 31P-n.m.r. confirmed the decrease in ATP and creatine phosphate concentrations and indicated a fall in intracellular pH. It is concluded that dinitrophenol-induced myopathy does not represent a good model for the human mitochondrial myopathic condition as has been previously suggested.

Long-term effects of estrogen on rat skeletal muscle

The long-term effects of estrogen on the development of rat extensor digitorum longus (EDL) and soleus (SOL) muscles were examined using physiological and histochemical methods. The rats were in three groups: group 1, ovariectomized; group 2, sham-operated; and group 3, ovariectomized followed by estradiol administration. Isometric twitch and tetanic tensions of both the EDL and SOL obtained from 10-week-old rats were evoked by electrical stimulation. The isometric twitch tensions of the EDL in groups 2 and 3 were significantly lower than in group 1, however, there were no significant differences in isometric twitch tensions of the SOL among the three groups. The isometric tetanic tensions of the EDL in groups 2 and 3 were also significantly lower than in group 1, and the isometric tetanic tension of the SOL in group 3 was significantly lower than in group 1. There were no changes in the total number of muscle fibers or in the ratios of fiber types. But the mean fiber diameter of all fiber types (particularly in types IIA and IIB) was significantly lower in group 3 than in groups 1 and 2. Therefore, the possibility that estrogen may play an inhibitory role in the development of skeletal muscle fibers has to be considered.

Influence of thyroid hormone levels on the electrical and mechanical properties of rabbit papillary muscle

We have examined the influence of chronic in vivo alterations of thyroxine levels on the electrophysiological and mechanical properties of rabbit ventricular papillary muscles measured in vitro. Marked changes in the repolarization phase of the action potential and the time to peak tension of isometric twitches were observed when thyroid hormone levels were increased above or decreased below normal. The time to peak tension was consistently shorter than normal in hyperthyroid and longer than normal in hypothyroid preparations. In hypothyroid preparations the action potential duration was greater than that of controls at all stimulation frequencies tested (0.1 to 1.0 Hz). In hyperthyroid preparations, the repolarization phase consisted of an initial phase of fast repolarization to membrane potential values between -20 and -40 mV followed by a plateau. The early phase of repolarization persisted at all stimulation frequencies tested (0.1 to 1.0 Hz) but the plateau component increased markedly as the stimulation frequency was decreased. The early phase of repolarization was markedly reduced in the presence of 4-aminopyridine. These results suggest that thyroxine levels may modulate the kinetics of a transient outward current which in rabbit papillary muscle normally is responsible for the frequency dependence of action potential duration. Action potential amplitude, maximum rate of rise, resting membrane potential, and peak isometric twitch tension were not markedly different between the three classes of preparations. A second depolarizing response occurred in all hyperthyroid preparations at low stimulation frequencies (0.1 to 0.4 Hz) but not in control or hypothyroid preparations. This second depolarizing response, which was eliminated by D-600 treatment, was similar to the calcium-dependent slow action potentials recorded in other cardiac preparations. These two component action potentials could represent either intrinsic single cell activity, or a re-entry wave of depolarization which results from nonhomogeneous excitation.

Myosin light chain kinases and myosin phosphorylation in skeletal muscle

Myosin light chain kinases appear to exist as a family of tissue- and species-specific isozymes. The skeletal muscle kinases, although differing widely in molecular weight among vertebrate species, are catalytically similar and antigenically related. The smooth muscle kinases are catalytically and antigenically distinct from the skeletal muscle kinases. The functional basis for the existence of myosin light chain kinase isozymes has not been determined. Phosphorylation of fast-twitch skeletal muscle myosin P-light chain occurs at physiologically relevant contraction frequencies and durations, and the extent of P-light chain phosphorylation correlates with enhancement of isometric twitch tension in fast-twitch muscle under a variety of experimental conditions. Phosphorylation of myosin P-light chain in vertebrate fast-twitch skeletal muscle may play a modulatory role in calcium regulation of muscle contractility.

Contractile responses of rat lateral gastrocnemius and soleus to dianabol (17β-hydroxy-17-methyl-1,4-androstadien-3-one) and exercise

Rats were maintained for 8 weeks on a program of twice weekly subcutaneous injections of 0.075 mg Dianabol (methandrostenolone) and treadmill running to investigate the ability of this compound to increase skeletal muscle contractility. The lateral gastrocnemius isometric twitch and tetanic tensions of the Dianabol Exercise group were both 1.5 times that of the Control animals. Treatment with either Dianabol or exercise alone did not affect the contractile strength of this muscle. The contractility of the soleus was not altered by any of the treatments employed. Withholding of steroid injections midway through the 8 week treatment period while maintaining exercise administration did not alter the effect observed in the Dianabol Exercise group. It is concluded from the results of this study that concomitant administration of Dianabol and exercise for 8 weeks can have a marked effect on isometric force characteristics of skeletal muscle in young adult male rats.

Myosin light chain phosphorylation in fast and slow skeletal muscles in situ.

The physiological properties of contraction-induced phosphate incorporation into the phosphorylatable light chain (P-light chain) of myosin were examined in fast-twitch white, fast-twitch red, and slow-twitch skeletal muscles in situ. Neural stimulation of rat gastrocnemius muscles between 0.5 and 100 Hz produced an increase in the phosphate content of the P-light chain from the white portion of the muscle, and the rate of P-light chain phosphorylation was frequency dependent. The extent of phosphorylation of P-light chain from the fast-twitch red portion of the gastrocnemius muscle was less. In contrast to fast-twitch skeletal muscle, only high-frequency stimulation (30-100 Hz) produced a small increase in the phosphate content of P-light chain from the slow-twitch soleus muscle. Fast white muscle contained 2.2 and 3.5 times more myosin light chain kinase activity than did the fast red and slow muscle, respectively. The rate of P-light chain dephosphorylation was four times faster in slow muscle than in fast white muscle. Thus the greater extent of phosphorylation of P-light chain in fast-twitch white skeletal muscle fibers may be due in part to the presence of more kinase and less phosphatase activities. Isometric twitch tension potentiation was correlated to the extent of phosphorylation of P-light chain from fast white muscle. The physiological consequences of P-light chain phosphorylation are likely to be of greatest importance in fast-twitch white muscle.

Effect of extracellular calcium on contractile activation in guinea-pig ventricular muscle.

The problem of whether or not the alterations in twitch tension of mammalian cardiac muscle induced by changes in extracellular Ca concentration ([Ca]o) are due to the Na-Ca exchange process across the surface membrane and/or the changes in the amount of Ca in the sarcoplasmic reticulum has been re-examined by using thin bundles (70-120 micron diameter) dissected from guinea-pig papillary muscle. The observed time course of the change in the twitch tension due to a step change in [Ca]o was compared with that computed on a basis of the diffusion process of Ca ions in a circular cylinder and of the steady-state relation between [Ca]o and twitch tension. After a sudden decrease in [Ca]o from 2 mM to various lower concentrations, the isometric twitch tension of the thin bundles first fell rapidly and monotonically and then showed a much smaller and slower secondary fall. The correspondence of the observed time course of the rapid phase with the predicted time course and the observed half-time of the rapid phase ranging from 1.0 to 2.5 s indicate that the rapidity of the twitch response may be dominated by simple diffusion of Ca ions through the extracellular space. If so, the effective diffusion constant of Ca ions inside the bundles was 1.4 +/- 0.2 X 10(-6) cm2/s (mean +/- S.E., n = 9). The magnitude and direction of the step change in [Ca]o or the change at different stimulus frequencies gave rise to dissimilar time courses of the contractile change; the difference in the rapid time courses due to these factors could be explained by the simple diffusion models, but not in the much slower phase. The half-time for the Ca effect was the same as that for the rapid effect of Na ions in the external solutions. The time course of twitch decline due to [Ca]o decrease in the Na-free (Li) solution was identical to that predicted from the time course measured in the Na-rich solution and the steady-state relation between [Ca]o and tension in the Na-free solution. The half-time of Ca leak from the sarcoplasmic reticulum in the skinned cardiac muscle was 40-60 s in the presence of 10 mM-EGTA, much shorter than that of the Ca leak in the skinned amphibian skeletal muscle, but much longer than that of twitch responses due to step changes in [Ca]o in the intact cardiac muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Recovery of reinnervating rat muscle after cast immobilization

We evaluated the recovery of the reinnervating rat plantar flexor muscles after different periods of casting and then decasting the lower extremities. Four groups of 4-month-old, female Wistar rats underwent bilateral crush-denervation of the sciatic nerve at the sciatic notch. Two weeks after nerve crush, the hind legs of three groups of rats were immobilized with bilateral casts at the knee and ankle joints and the fourth group was a control group. Of the three casted groups, one was mobilized after 1 week and another group after 3 weeks of casting. The third experimental group remained casted until the end of 6 weeks. Six weeks after the nerve crush, all groups were evaluated for muscle weights of the soleus, plantaris, and gastrocnemius; absolute amounts of the myofibrillar, sarcoplasmic, and stromal proteins in the gastrocnemius; the fiber diameters and percent composition of type I and type II fibers in the soleus and plantaris; and the isometric contractile properties of the soleus muscle. Compared with the denervated control group, the experimental groups revealed the following: (i) Four weeks of casting caused a reduction in wet weight (range 30.6 to 40.4%, P < 0.01) in the soleus, plantaris, and gastrocnemius muscles. Decasting led to an earlier recovery of the soleus than of the plantaris and gastrocnemius muscles. (ii) The myofibrillar protein returned to control values with 3 weeks of decasting but the stromal protein remained significantly elevated and the sarcoplasmic protein significantly depressed regardless of the period of mobilization. (iii) Except for the type I fibers in the plantaris, the remainder of the muscle fibers in the soleus and plantaris decreased in size due to casting. Only the type I muscle fibers of the soleus increased in size with longer periods of mobilization. (iv) Four weeks of casting significantly altered the maximum isometric twitch tension (−42.3%), contraction time (+17.1%), maximum tetanic tension (−38.1%), and half-fatigue time (+40.5%) in the soleus. The reinnervating soleus muscle appears to recover from the effects of casting sooner than the plantaris or gastrocnemius muscles.

Mechanical properties of muscles from Xenopus borealis following maintenance in organ culture

1. 1. The mechanical properties of sartorii muscles from the toad Xenopus borealis were studied in organ cultures lasting up to 26 days. 2. 2. Isometric twitch and tetanic tensions diminished in force reaching half their initial values after 15 days in culture. In contrast, twitch time to peak time to half relaxation, twitch-tetanus ratio and muscle weight-body weight ratio, were unchanged. 3. 3. Maximum isotonie shortening velocity ( V max) declined, with a half time similar to that of the isometric force. 4. 4. The fall in isometric tension is probably due to a breakdown of activation in some fibres. The change in V max could be due to a loss of functional sarcomeres in series with the tendons.

Evoked responses in normal and diseased muscle with particular reference to twitch potentiation.

The compound muscle action potential and isometric twitch tension evoked by single and repetitive electrical stimuli are indicators of the number of motor units activated and of the contractile properties of the muscle. The action potentials and mechanical responses were recorded in proximal and distal muscles in patients with myasthenia gravis and myopathy and compared with findings in normal subjects. In normal muscle, at low rates of stimulation (2-3 s-1) the decrement was at most 5% in the action potential and 15-24% in the twitch tension. Tetanic stimuli (50 s-1) were unsuitable for diagnostic purposes because of movement artefact. In patients with myasthenia gravis, the incidence and size of the decrement of evoked responses were greater in the platysma than in the elbow flexors and the adductor pollicis (ADP) muscles. The 2-3 times greater post-tetanic facilitation (PTF) of the action potential in the platysma than in extremity muscles also indicates a more severe functional block in facial muscle. The PTF is an indicator of recruitment of blocked fibres. The maximal decrement was grossly related to the titre of antibodies against the acetylcholine receptor. To reveal failure of neuromuscular transmission in patients with myasthenia gravis without a decrement, a small dose of d-tubocurarine (0.2 mg in 30 ml of saline) was injected i.v. in the upper arm in a regional curare test. The sensitivity was greater in patients with myasthenia gravis than in controls and in patients with myopathy. Potentiation of twitch tension reflects contractile properties. In normal muscle twitch potentiation in the staircase (1-3 s-1, 100 s in duration) and after tetanus (50 s-1, 1.5 s in duration) was 2-3 times greater in the platysma than in the elbow flexors and ADP, presumably related to the greater proportion of fast-twitch fibers in facial muscle. The amplitude of the action potential and the twitch tension varied proportionally with the number of fibers activated and the difference in the decrements of the action potential and the twitch during the staircase in some patients with myasthenia gravis showed that the staircase phenomenon was diminished suggesting abnormalities in the excitation-contraction coupling. The diminution of the staircase and post-tetanic potentiation (PTP) in myopathy also indicates impairment of the excitation-contraction coupling. In rats with severe chronic myasthenia gravis, the staircase and PTP were decreased even when the failing neuromuscular transmission was circumvented by applying direct stimuli to the extensor digitorum longus muscle (EDL).

Compensatory hypertrophy of the soleus in tumor-bearing rats

Compensatory hypertrophy of the rat soleus was compared between normal rats (N) and rats bearing a non-metastasizing mammary tumor (TB). Two weeks after the tumor inoculation, introduced subcutaneously on the midline of the upper back, the two groups of rats underwent unilateral tenotomy of the plantaris and gastrocnemius muscles to induce functional overload or compensatory hypertrophy of the soleus. One week later, the body weight (BW), wet muscle weights (MW), percent of Type I (slow-twitch) and Type II (fast-twitch) muscle fibers and contractile parameters of the isometric twitch (P t) and tetanic (P o) tensions were evaluated. The TB animals did not show any signs of cancer cachexia. The sham-operated control soleus muscles of the two groups were similar in wet MW, maximum isometric P t and P o. The latent period (LP), the contraction time (CT), the half relaxation time (HRT) and the number of Type I (slow-twitch) fibers were increased significantly. The hypertrophied muscles in the N and TB rats showed significant declines in the maximum isometric P t, compared to their respective controls. These data suggest that the compensatory hypertrophy of muscle is expressed similarly in both the normal and tumor-bearing rats but that it interferes with the generation of isometric twitch tension in the muscle.