Endurance training increases acetylcholine receptor quantity at neuromuscular junctions of adult rat skeletal muscle

The aim of the study was to test the hypothesis that a 16 week endurance training program would alter the abundance of endplate-associated nicotinic acetylcholine receptors (nAChR) in various rat skeletal muscles. We found a 20% increase in endplate-specific [125I]alpha-bungarotoxin binding in several muscles of trained rats, accompanied by equal susceptibility of toxin binding to the inhibitory effect of D-tubocurarine in sedentary and trained muscles. We conclude that the neuromuscular junction adaptations that occur with increased chronic activation include an increase in nAChR number. Results of experiments designed to determine nAChR turnover also suggest that this effect is mediated by an alteration in the receptor's metabolic state. The potential implications and mechanisms of this adaptation are discussed.     

Effect of strength training on EMG of human skeletal muscle

An 8-year-old white girl with a history of vertigo, nausea, and vomiting developed a progressive hearing loss, bilateral retinal arteriolar narrowing in each eye, vasoproliferation, and subsequent intravitreal hemorrhage. An attempt at peripheral retinal ablation with cryotherapy in the left eye resulted in retinal detachment. Spontaneous retinal detachment occurred in the right eye and was successfully repaired. Repeated intermittent hemorrhages occurred despite intraocular diathermy. Three years after onset, visual acuity was R.E.: 6/21 (20/66) and L.E.: light perception. She remains totally deaf. A 20-year-old white woman developed severe bilateral sensorineural hearing loss with poorly functioning labyrinths, followed by midperipheral retinal arteriolar occlusions and vasoproliferation on the optic nerve head. Progressive retinal neovascularization was followed by rubeosis iridis and repeated episodes of intravitreal bleeding. Six years after onset, visula acuity was R.E.: hand motions, and L.E.: 6/3 (20/100). She remains totally deaf. Both patients were of normal gestation, development, and mentality, without evidence of other systemic disease. The cause of this disease was not found.     

The case for adaptability of the neuromuscular junction to endurance exercise training

Although the adaptability of the neuromuscular junction (NMJ) has been demonstrated using the models of denervation/reinnervation, electrical stimulation, development, aging, and pathological states, relatively little is known about the effects of increased chronic voluntary use on the morphology and physiological function of the NMJ. A review of findings relating to adaptations in the various pre- and postsynaptic components of the NMJ with exercise training is presented. These findings are discussed as they pertain to NMJ function during exercise. Other physiological modulators of the NMJ, such as trophic factors released by nerve terminals and muscles, and circulating substances are discussed in terms of possible roles they may play in training-induced adaptations.     

Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers

Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.     

Absence of an effect of fatigue on muscle efficiency during high-intensity exercise in rat skeletal muscle

The effect of fatigue was studied on rat skeletal muscle efficiency during maximal dynamic exercise of 10s duration. After the initial 4s of exercise, power output decreased rapidly to 46.2 +/- 6.7% (mean +/- SD; n = 6) after 6s of stimulation and further to 17.5 +/- 5.8% in the last contraction. Both the rates of total work output and high-energy phosphate consumption decreased with increasing exercise duration. As a result muscle efficiency was not affected by exercise time in the present experiments. This result indicates that fatigue in severe maximal exercise is induced by a feed-back mechanism, which in the case of high ATP utilisation rates will reduce ATP splitting probably by reducing Ca(2+)-release from the sarcoplasmic reticulum.     

Effects of exercise training in the elderly: impact of progressive- resistance training on skeletal muscle and whole-body protein metabolism

The declines in functional capacity and muscle function with advancing age are well-documented. In addition, it appears that the age-related changes in body composition have profound effects on functional capacity and nutrient requirements. The overwhelming evidence presented in the present review suggests that the loss of muscle strength and function observed with advancing age is reversible even in the frail elderly. Along with the profound functional improvement in older individuals in response to progressive-resistance training, several studies have reported increases in resting energy expenditure and increased requirements for dietary protein. Exercise programmes designed to improve muscle strength be recommended for older individuals as an effective countermeasure to the sarcopenia of old age.     

Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix

The purpose of this study was to evaluate the effect of endurance exercise training on both locomotor skeletal muscle collagen characteristics and passive stiffness properties in the young adult and old rat. Young (3-mo-old) and senescent (23-mo-old) male Fischer 344 rats were randomly assigned to either a control or exercise training group [young control (YC), old control (OC), young trained (YT), old trained (OT)]. Exercise training consisted of treadmill running at approximately 70% of maximal oxygen consumption (45 min/day, 5 days/wk, for 10 wk). Passive stiffness (stress/strain) of the soleus (Sol) muscle from all four groups was subsequently measured in vitro at 26 degreesC. Stiffness was significantly greater for Sol muscles in OC rats compared with YC rats, but in OT rats exercise training resulted in muscles with stiffness characteristics not different from those in YC rats. Sol muscle collagen concentration and the level of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP) significantly increased from young adulthood to senescence. Although training had no effect on Sol muscle collagen concentration in either age group, it resulted in a significant reduction in the level of Sol muscle HP in OT rats. In contrast, exercise had no effect on HP in the YT animals. These findings indicate that 10 wk of endurance exercise significantly alter the passive viscoelastic properties of Sol muscle in old but not in young adult rats. The coincidental reduction in the principal collagen cross-link HP also observed in response to training in OT muscle highlights the potential role of collagen in influencing passive muscle viscoelastic properties.     

Effects of muscle electrical activity on the transmission of developing neuromuscular junction

A prospective cohort study in a neonatal intensive care unit (ICU) was carried out to evaluate whether the incidence of infection in neonates receiving intestinal decolonization was reduced in comparison to those who did not. This study was performed after controling possible confounding infection risk factors. A total of 536 babies were screened in our ICU during the 27-month study period. Neonates were admitted to the ICU for different reasons: low weight, respiratory distress syndrome, acute fetal suffering, surgery, etc. The doctor in charge decided whether the baby should be decolonized or not, so this experimental study was non-random. Thus more of the babies with a greater risk of infection were decolonized more often than the other babies who were not so much at risk. In this study, babies were classified by type of decolonization given: a well-performed Selective Intestinal Decolonization (SID) was done (early and with three oral drugs: E polymyxin, tobramycin and nystatin): 10.8% of the babies; Incorrect SID (was begun late and/or less than three drugs were used): 16.7% of the babies; and Without SID (72.9%). Total nosocomial infection (NI) was 11.2%, catheter-associated sepsis was 42% of the total NI. When the NI incidence was directly compared among groups, it was lower in the group without SID, but infants with decolonization initially had more infection risk factor than the first group. For this reason, multiple logistic regression was used in order to stratify factors by infection probability, and correcting the existing bias.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of skeletal muscle perfusion during exercise

OBJECTIVE: To compare the composition and mechanical properties of the newly developed bladder acellular matrix graft (BAMG) with the normal urinary bladder in rat, pig and human. MATERIALS AND METHODS: Rat, pig and human urinary bladders were harvested and divided into control and experimental groups. For the latter, BAMGs were prepared, and light and transmission electron microscopic studies performed. Strips from the normal bladders and the BAMGs (10 in each group) were tested under tension, and the ultimate tensile strength, maximum strain, and elastic modulus were determined from stress/strain curves. RESULTS: Both types I and III collagen, as well as elastic fibres, were observed as major components of the matrix scaffold. There were more collagen type I fibres in the rat than in the pig and human BAMGs, whereas the pig, and particularly the human, both showed higher levels of type III collagen and elastic fibres. These different matrix scaffold patterns were confirmed by electron microscopy. Results from biomechanical testing showed no significant differences for strength, strain or elastic modulus between BAMG and control bladder strips, except in the rat where the maximum strain values were significantly lower. CONCLUSION: There are variations in the acellular matrix structure with similar biomechanical properties between the BAMG and the normal urinary bladder in three different species. These results may underscore the potential of the BAMG. Furthermore, this in vitro model provides a suitable method to study the mechanical properties of the urinary bladder and may serve as a diagnostic tool for various investigations.     

Functional morphology of serially linked skeletal muscle fibers

In the skeletal muscle fiber organization of many vertebrate muscles, serial arrangements or linkages of muscle fibers along the muscle or fascicle are commonly found. These serially linked muscle fibers employ distinct junctional morphologies from muscle to muscle. Notable are the end-to-end linkages of muscle fibers through tendinous intersections (TIs), where many fibers end onto a continuous connective tissue plate with folded terminations similar to myotendinous junctions. Besides this end-to-end linkage, overlapping linkages or arrangements occur among nonspanning fibers terminating intrafascicularly. These nonspanning fibers bear tapering terminations with direct cell-cell (myomuscular) junctions or without any specialized junctions. Despite their overlapping linkages or tapering profiles, nonspanning fibers maintain a uniform sarcomere length along the linked fibers, suggesting that the overlapping-linked nonspanning fibers are equivalent to the end-to-end linked fibers in their mechanical capacity. However, the junctional compliance could differ in their extracellular elastic components and their organization at junctional sites, e.g., direct mechanical (myomuscular) junctions vs. indirect linkages through connective tissue. Increasing evidence suggests that the elastic components, including muscle fibers as well as connective tissues, are more critical than previously thought for the mode and/or the efficiency of tension transmission among serially arranged fibers and thus for the mechanical properties of the muscle.     

Differential susceptibility of diaphragm muscle fibers to neuromuscular transmission failure

The pattern of glycogen utilization was used to determine whether various muscle fiber types in the rat diaphragm are differentially susceptible to neuromuscular transmission failure. Muscle segments from the midcostal region were repetitively stimulated directly or via the phrenic nerve at 10 or 75 Hz. Muscle fiber types were classified histochemically as type I, IIa, or IIb. The amount of muscle fiber glycogen depletion with direct stimulation depended on stimulation rate (75 Hz > 10 Hz) and fiber type (IIb > IIa > I). However, with nerve stimulation, muscle fiber glycogen depletion did not display the same dependency on stimulation rate (10 Hz > 75 Hz), although with stimulation at 10 Hz, the same rank order of fiber depletion was observed (IIb > IIa > I). This rank order of depletion was reversed (I > IIa > IIb) during repetitive stimulation of the nerve at 75 Hz. By intermittently stimulating the muscle directly during continuous nerve stimulation, we determined that neuromuscular transmission failure contributed significantly to the force decline after 2 min of stimulation at 75 Hz but relatively little to the force decline after 2 min of stimulation at 10 Hz. A significantly greater fraction of the force decline could be attributed to neuromuscular transmission failure with repetitive bouts of stimulation at 10 Hz. We conclude that neuromuscular transmission failure causes a significant portion of the force decline after 8 min of stimulation at 10 and 75 Hz, that all diaphragm fiber types are susceptible to neuromuscular transmission failure, but that type IIb fibers are particularly susceptible at higher frequencies of stimulation.     

Autonomic control of skeletal muscle vasodilation during exercise

Despite extensive investigation, the control of blood flow during dynamic exercise is not fully understood. The purpose of this study was to determine whether beta-adrenergic or muscarinic receptors are involved in the vasodilation in exercising skeletal muscle. Six mongrel dogs were instrumented with ultrasonic flow probes on both external iliac arteries and with a catheter in a branch of one femoral artery. The dogs exercised on a treadmill at 6 miles/h while drugs were injected intra-arterially into one hindlimb. Isoproterenol (0.2 microg) or acetylcholine (1 microg) elicited increases in iliac blood flow of 89.8 +/- 14.4 and 95.6 +/- 17.4%, respectively, without affecting systemic blood pressure or blood flow in the contralateral iliac artery. Intra-arterial propranolol (1 mg) or atropine (500 microg) had no effect on iliac blood flow, although they abolished the isoproterenol and acetylcholine-induced increases in iliac blood flow. These data indicate that exogenous activation of beta-adrenergic or muscarinic receptors in the hindlimb vasculature increases blood flow to dynamically exercising muscle. More importantly, because neither propranolol nor atropine affected iliac blood flow, we conclude that beta-adrenergic and muscarinic receptors are not involved in the control of blood flow to skeletal muscle during moderate steady-state dynamic exercise in dogs.     

Myosin heavy chain composition in young and old rat skeletal muscle: effects of endurance exercise

The objective of this study was to determine the effects of age and exercise on the myosin heavy chain (MHC) composition of skeletal muscle. Young (3 mo) and old (22 mo) female specific pathogen-free barrier-reared Fischer 344 rats were randomly assigned to young untrained or young trained and old untrained or old trained groups, respectively. Young trained and old trained animals performed endurance exercise training on a motorized treadmill for 8 wk. Succinate dehydrogenase activity and MHC isoforms were measured in the plantaris (Plan), lateral and medial gastrocnemius (Gast), and soleus (Sol) muscles. In sedentary animals, aging resulted in a decrease (P < 0.05) in type IIb MHC and an increase (P < 0.05) in type IIa MHC in both the Gast and Plan muscles. Also, aging resulted in a small but significant increase (approximately 4%; P < 0.05) in type I MHC in the Sol. Exercise training resulted in significant (P < 0.05) increases in Gast, Plan, and Sol succinate dehydrogenase activity in both young and old animals. Furthermore, exercise training resulted in a decrease (P < 0.05) in the percentage of type IIb MHC and an increase (P < 0.05) in the percentage of type IIa MHC in the Plan in both young and old animals. These data suggest that there is an age-related shift in locomotor muscle MHC isoforms from a faster to a slower isoform.     

2 types of neuromuscular junction in the pharyngeal retractor muscle of snails

The pharyngeal retractor muscle of Helix lucorum is innervated by two symmetrical nerves which contain axons of two types forming myoneural junctions with the muscle cells. Type I junctions correspond to thick axons. These axon terminals which contain a large number of spherical, clear vesicles (41 +/- 5 nm) and a smaller number of dense-cored vesicles (67 +/- 3 nm) make contacts mainly with noncontractile sarcoplasmic processes of muscle cells. Type II junctions correspond to thin axons containing many of granules. Their axon terminals contact with contractile parts of muscle cells and contain a heterogenous population of vesicles: small spherical clear vesicles (44 +/- 2 nm), dense-cored vesicles and numerous irregularly outlined granules with fine-granular content (135 +/- 5 nm). Space between muscle cell is usually wide (50 nm and more) with the exception of sarcoplasmic processes where the gap may be less than 10 nm.     

Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training

After running training, which increased GLUT-4 protein content in rat skeletal muscle by <40% compared with control rats, the training effect on insulin-stimulated maximal glucose transport (insulin responsiveness) in skeletal muscle was short lived (24 h). A recent study reported that GLUT-4 protein content in rat epitrochlearis muscle increased dramatically ( approximately 2-fold) after swimming training (J.-M. Ren, C. F. Semenkovich, E. A. Gulve, J. Gao, and J. O. Holloszy. J. Biol. Chem. 269, 14396-14401, 1994). Because GLUT-4 protein content is known to be closely related to skeletal muscle insulin responsiveness, we thought it possible that the training effect on insulin responsiveness may remain for >24 h after swimming training if GLUT-4 protein content decreases gradually from the relatively high level and still remains higher than control level for >24 h after swimming training. Therefore, we examined this possibility. Male Sprague-Dawley rats swam 2 h a day for 5 days with a weight equal to 2% of body mass. Approximately 18, 42, and 90 h after cessation of training, GLUT-4 protein concentration and 2-[1,2-3H]deoxy-D-glucose transport in the presence of a maximally stimulating concentration of insulin (2 mU/ml) were examined by using incubated epitrochlearis muscle preparation. Swimming training increased GLUT-4 protein concentration and insulin responsiveness by 87 and 85%, respectively, relative to age-matched controls when examined 18 h after training. Forty-two hours after training, GLUT-4 protein concentration and insulin responsiveness were still higher by 52 and 51%, respectively, in muscle from trained rats compared with control. GLUT-4 protein concentration and insulin responsiveness in trained muscle returned to sedentary control level within 90 h after training. We conclude that 1) the change in insulin responsiveness during detraining is directly related to muscle GLUT-4 protein content, and 2) consequently, the greater the increase in GLUT-4 protein content that is induced by training, the longer an effect on insulin responsiveness persists after the training.     

Capillary supply of skeletal muscle fibers in untrained and endurance-trained men

Muscle fiber diameters and numbers of capillaries per fiber, per square millimeter, and around each fiber were determined in needle biopsies from the lateral part of the quadriceps muscle of 23 young men. Twelve subjects were untrained (UT) and eleven were endurance-trained (ET) athletes. Average values for maximal oxygen uptake were 51.3 (UT) and 72.0 ml/kg-min (ET). Mean fiber diameters were not significantly different in the two groups (48.8 and 49.1 micron). The capillaries per fiber ratios were 1.77+/-0.10 and 2.49+/-0.08 (mean+/-SE) in the UT and ET groups, respectively. The numbers of capillaries around each fiber were 4.43+/-0.19 (UT) and 5.87+/-0.18 (ET). The numbers of capillaries per mm2 were 585+/-40 (UT) and 821+/-28 (ET). Fiber diameters were 28% smaller in ultrathin than in fresh-frozen sections from the same biopsies. After correction for this difference, the numbers of capillaries per mm2 were 305 and 425 in the UT and ET, respectively. The capillaries per fiber ratio increased with increasing fiber diameter, but not sufficiently to maintain the number of capillaries per mm2. Fibers containing many mitochondria are surrounded by more capillaries than fibers with few mitochondria.     

Effects of an anabolic steroid and sprint training on selected histochemical and morphological observations in rat skeletal muscle types

The effects on selected histochemical and morphological parameters of anabolic steroid administration and of high-intensity sprint running, separately, and in combination, were studied in young adult male rats. Dianabol (methandrostenolone) 1 mg/day for 8 weeks had no significant effects on phosphorylase or glycogen staining intensities and on fiber area in skeletal muscles of either trained or sedentary animals. The program of sprint training resulted in significantly decreased intensities of phosphorylase in all ten regions of the gastrocnemius, plantaris, and soleus muscles that were studied. Glycogen localization was significantly increased with training in five regions of the gastrocnemius and plantaris muscles which contained predominantly fast-switch fibers. No changes in fiber area occurred with the training program. We conclude from these results that (a) normal androgen levels in young, healthy male animals are sufficiently high so that the intake of large doses of anabolic steroid does not result in the stimulation of glycogen metabolism or hypertrophy of skeletal muscle; (b) the changes induced by high-intensity, short-duration sprint training suggest that the existing glycolytic capacity of muscle is adequate to supply the muscles energy needs even during the stress of very strenous exercise, and that more fast-twitch fibers were recruited by the exercise regimen than slow-twitch fibers.     

The effect of autografting on the myosin composition in skeletal muscle fibers

The purpose of the study was to investigate the changes in myosin heavy chain (MHC) and myosin light chain (MLC) isoforms following autotransplantation of extensor digitorum longus muscles. Muscles were grafted in "standard" and "nerve-intact" conditions. MHC and MLC isoforms were analyzed by sodium dodecyl sulphate gel electrophoresis. Changes in MHC isoforms 10, 30, and 60 days after grafting were similar in the "standard" and the "nerve-intact" grafts. In contrast to MHC, changes in MLC were different in the 10th day groups, but the same in the 30th day groups. Sixty days after grafting the content of MLC isoforms was the same as the control muscles. These data indicate that transient loss of functional innervation, even for a short time, has permanent effect on the composition of MHC but not MLC isoforms in regenerating skeletal muscle fibers.     

Capillary adrenoceptors in rat skeletal muscle

Coronary artery disease (CAD) is the most common cause of death in women in the United States. Dyslipidemia is a risk factor for CAD in both men and women. Low levels of high-density lipoprotein (HDL) cholesterol and hypertriglyceridemia, especially in association with a dense low-density lipoprotein (LDL) phenotype, may be of greater importance in women than in men. The relationship between CAD and dyslipidemia and the therapeutic approach to disorders of lipid metabolism in women have unique features because of the effects of exogenous and endogenous hormones on lipid pathways. Estrogen decreases LDL cholesterol and Lp(a) lipoprotein and increases triglyceride and HDL cholesterol levels. Progestogens decrease triglycerides, HDL cholesterol, and Lp(a), and they increase LDL cholesterol. Thus, oral contraceptives increase plasma triglycerides, whereas the effect of these agents on LDL cholesterol and HDL cholesterol levels is related to the androgenicity and dose of progestogen. Postmenopausal hormone replacement therapy increases triglycerides and decreases LDL cholesterol. The effect of hormone replacement therapy on HDL cholesterol is influenced by the addition of progestogen. Although no primary prevention studies have analyzed lipid lowering and CAD in women, secondary prevention studies have suggested that the response to drug treatment and the benefit of lipid lowering are similar in women and in men. Hormone replacement therapy should be considered in the treatment of hypercholesterolemia in postmenopausal women; however, individualization of treatment is important to avoid adverse effects.     

The influence of skeletal muscle incubation medium on fatigue of neuromuscular preparation and on transmitter release at neuromuscular junctions in the frog

The effect of frog skeletal muscle incubate on fatigue was studied in frog sciatic nerve, sartorius muscle preparation. Fatigue was produced by prolonged repetitive (1 s-1) stimulation of motor nerve or of curarized muscle. The incubate partially restored isometric contraction amplitudes of muscle fatigued by nerve stimulation. This effect of partial recovery from fatigue (PRF effect) was exerted mainly by a relatively low-molecular fraction (LMF; < 10 kDa) of the incubate. The incubate and its fractions failed to produce the PRF effect in experiments with directly stimulated muscle. The action of LMF on synaptic transmission in unfatigued cutaneous-pectoris muscle was examined using binomial analysis of quantal transmitter release. LMF produced an increase in the end-plate potential quantal content (m) at synapses with low initial m values. In contrast, it produced a decrease i n m at synapses with higher m values. Both effects were due to respective changes in binomial parameter n. It is assumed that the stimulatory presynaptic action of the incubate on synapses the effectiveness of which was lowered during fatigue, could account for the PRF effect. A possible contribution of low- and high-molecular components of the incubate is discussed.