In-vitro stimulation on the rat epitrochlearis muscle. II. Effects of catecholamines and nutrients on protein degradation and amino acid metabolism

The influence of catecholamines and branched-chain amino acids (BCAA) plus insulin on protein degradation and amino acid metabolism was investigated in isolated and electrically stimulated rat epitrochlearis muscles. 10(-7) M adrenaline significantly increased the total amount of muscle tyrosine during 40 min of stimulation with 50 Hz (I s min 1) pulse trains. On the other hand, BCAA + insulin at normal and five times normal plasma concentrations had no effect on muscle tyrosine. Muscle 3- methylhistidine was not influenced by any of the treatments. Muscle release and content of aspartate, alanine, glutamate and glutamine showed individual response characteristics to catecholamines and BCAA + insulin. The data indicate that adrenaline can induce an increased total protein degradation in rat fast muscle during acute contractions in vitro and, furthermore, that BCAA + insulin does not retard protein breakdown during acute muscle contraction.     

The effects of high-intensity exercise on skeletal muscle neutrophil myeloperoxidase in untrained and trained rats

The primary purpose of this study was to examine the effects of high-intensity acute exercise on neutrophil infiltration in different muscle fiber types of untrained rats and to compare postexercise neutrophil accumulation in muscles of untrained and trained animals. The effect of high-intensity acute exercise on blood neutrophil degranulation reaction in trained animals was also elucidated. Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil migration into muscles and blood neutrophil degranulation. Male albino rats were subjected to acute exercise and 5 weeks of training. The used model of intensive acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma and neutrophils was determined 48-h following the completion of a training process. In addition, MPO content in the trained rats was measured immediately (in blood plasma and neutrophils) after and 24 h (in muscles) following a single-bout of exercise to exhaustion. The remaining two-third of the trained animals were exposed to a single-bout of nonstop swimming with the addition of 6% body mass until exhaustion. These animals were sacrificed immediately and 24 h after loaded swimming to analyze leukocyte count, MPO content in blood plasma and neutrophils and in muscles, respectively. About 24 h after exercise MPO concentrations in the red portion of quadriceps muscle and in soleus muscle were 4–7-fold higher as compared to the white portion of m. quadriceps. There was an association between the quantity of repetitive bouts of swimming and MPO content in the muscles. The duration of swimming to exhaustion of trained rats was 3.8-fold longer than untrained sedentary control. At rest, plasma MPO concentration was found to be 40% higher in trained rats compared to untrained controls (P < 0.05). Postexercise plasma MPO concentrations were significantly higher both in untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting values. At rest neutrophil MPO concentration was found to be 33% lower in trained rats compared to untrained controls (P < 0.05). There were no significant differences in muscle MPO concentrations between untrained and trained rats at rest. A single-bout of exercise to exhaustion produced a greater increase in MPO content in untrained compared to trained rats. The data suggest that postexercise neutrophil infiltration is more intensive in red fibers types compared to white fiber types. A smaller neutrophil infiltration in muscles of trained animals after exhaustive exercise suggests a protective effect of previous training to muscle injury.Portions of this paper were presented by V. Morozov in 2003 at the 6th ISEI Symposium on Exercise Muscle Metabolism and Immune Function, Copenhagen.     

In-vitro stimulation of the rat epitrochlearis muscle. II. Effects of catecholamines and nutrients on protein degradation and amino acid metabolism

The influence of catecholamines and branched-chain amino acids (BCAA) plus insulin on protein degradation and amino acid metabolism was investigated in isolated and electrically stimulated rat epitrochlearis muscles. 10^-7m adrenaline significantly increased the total amount of muscle tyrosine during 40 min of stimulation with 50 Hz (1 s min^-1) pulse trains. On the other hand, BCAA + insulin at normal and five times normal plasma concentrations had no effect on muscle tyrosine. Muscle 3-methylhistidine was not influenced by any of the treatments. Muscle release and content of aspartate, alanine, glutamate and glutamine showed individual response characteristics to catecholamines and BCAA + insulin. The data indicate that adrenaline can induce an increased total protein degradation in rat fast muscle during acute contractions in vitro and, furthermore, that BCAA + insulin does not retard protein breakdown during acute muscle contraction.     

Augmented glucose uptake and amino acid release by muscle underlying the burn wound and their moderation by ketone bodies

Glucose uptake and amino acid release by skeletal muscle from the burned and unburned regions of the body were compared in the presence or absence of ketone bodies. Rats were scalded on one hind limb and, 3 days later, soleus muscles from the burned and unburned limbs of burned rats as well as from controls were incubated in Krebs-Ringer bicarbonate medium with 10 mM glucose. Acetoacetate (5 mM) or β-hydroxybutyrate (10 mM) was included as necessary. In the absence of ketones, burned limb muscles took up, on the average, 85% (P < 0.002) more glucose and released 110% (P < 0.001) more alanine, 67% (P < 0.002) more glutamate, and 54% (P < 0.002) more glutamine than controls. The unburned limb muscles of burned rats usually did not differ from controls. Acetoacetate depressed glucose uptake in all groups of muscles by a comparable absolute amount, which represented a drop of 33% (P < 0.02) in burned limb muscles and 64% (P < 0.04) in both types of uninjured muscles. Alanine release was depressed about 15% (P < 0.03) in all muscle groups. β-Hydroxybutyrate produced depressions in glucose uptake and alanine release by both types of uninjured muscles but similar effects on burned limb muscles were not statistically significant. Neither ketone had any appreciable effect on glutamate or glutamine release by any muscle group. It is concluded that glucose uptake and the release of alanine, glutamate, and glutamine are chronically increased in skeletal muscle from the burned but not the unburned region of the rat. Both acetoacetate and β-hydroxybutyrate depress glucose uptake and alanine release by muscle remote from the injured region but only acetoacetate exhibited this effect in metabolically altered muscle underlying the burn wound.     

In-vitro stimulation of the rat epitrochlearis muscle. I. Contractile activity per se affects myofibrillar protein degradation and amino acid metabolism

The influence of contractile activity on protein degradation and amino acid metabolism in skeletal muscle was investigated by utilizing an in-vitro electrical stimulation model with the rat epitrochlearis muscle preparation. Graded decreases in contraction force and in the muscle content of ATP and PCr, and increases in lactate were recorded with different rates of stimulation (1 h) and with both isometric twitches and tetanic contractions. 3-Methylhistidine and phenylalanine were chosen as indicators of myofibrillar and total protein degradation, respectively. The release of 3-methylhistidine was significantly stimulated by contractile activity, but a significant increase in the total amount of this amino acid (released amount + tissue content) occurred only at the most intense contraction rates. The release rate, tissue content and total amount of phenylalanine were not influenced by the contractions. Glutamate formation was generally inhibited, but its release was increased. Alanine synthesis was increased in moderately and intensely stimulated muscles. Glutamine and glycine were not influenced by the contractions, however. Inhibition of protein synthesis did not significantly influence protein degradation or amino acid release. The data suggest that in the absence of anabolic factors in the medium, myofibrillar protein degradation is increased in heavily activated muscle. This takes place without total protein breakdown being affected.     

Free amino acids in muscle tissue and plasma during exercise in man

Blood and muscle samples (percutaneous biopsy of m. quadriceps femoris) were taken before exercise and after 10 and 20 min of exercise in four healthy subjects working on a bicycle ergometer with a load of 70% of Vo2 max. Free amino acids were determined in plasma and muscle and the intracellular concentration of each amino acid was calculated by the chloride method. The plasma concentration of alanine, arginine and glutamine increased during exercise. In muscle there was an increase in glutamine and alanine concentration and a decrease in glutamate concentration at 10 min of exercise; after 20 min of exercise the increase in alanine and glutamine concentrations was less marked, but the decrease in glutamate concentration was of a similar magnitude. The results demonstrate that glutamate is a quantitatively important ammonia acceptor during heavy exercise.     

Differential variation of mitochondrial H2O2 release during aging in oxidative and glycolytic muscles in rats

Mitochondrial free radical (ROS) production could be involved in sarcopenia. Our aim was to measure this production in various muscles during aging. Male Wistar rats aged 4.5 and 24 months were used. H(2)O(2) release and protein carbonyls were evaluated in isolated mitochondria from an oxidative (soleus) and a glycolytic (tibialis anterior) muscle. Total and Mn-superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) activities were measured in tibialis anterior. In soleus, glutamate/malate supported mitochondrial H(2)O(2) release was lower than in tibialis anterior in young rats, but increased significantly with age. In tibialis anterior, glutamate/malate or succinate supported H(2)O(2) release was unchanged with age. ROS generators were complexes I and III. Mitochondrial carbonyl content remained stable during aging in both muscles but tended to be higher in tibialis anterior than in soleus. Tibialis anterior total SOD (+17%), catalase (+84%), and GPX (-17%) activities varied significantly with age but Mn-SOD was unchanged, suggesting an increase in cytosolic ROS production. In conclusion, the higher life-long H(2)O(2) release observed in tibialis anterior is consistent with the known sensitivity of glycolytic muscles to sarcopenia. The fact that the rate of H(2)O(2) release increases with age in soleus seems to have little impact.     

Influence of glial cells in the dopamine releasing effect resulting from the stimulation of striatal δ-opioid receptors

Recent data indicate that striatal dopamine release induced by stimulation of δ-opioid receptors is a consequence of glutamate release. However, glial cells, which mainly support glutamate uptake and are involved in glutamate signaling and potentially express δ-opioid receptors, could participate to this effect. The present study investigates the contribution of glial cells in the releasing effects of [d-Pen2, d-Pen5]-enkephalin (DPDPE) by using the gliotoxin l-α-aminoadipate (l-αAA). Initially, we evaluated the early influence of l-αAA local infusion (10 μg/μL) on dialysate levels of glutamate and dopamine under basal or DPDPE treatment conditions. l-αAA produced a significant increase of glutamate and dopamine in dialysates (+76% and +50% respectively) and the concomitant infusion of DPDPE (10 μM) significantly enhanced this effect in an additive manner (+110% and +44% respectively). Secondly, we assessed the DPDPE effects on striatal glutamate and dopamine dialysate levels, 2 days after an intra-striatal injection of l-αAA which produced destruction of glial cells. This lesion, decreasing the basal glutamate dialysate level as well as its tissue content (by 55% and 36% respectively), prevented the increase in glutamate and dopamine extracellular levels induced by DPDPE. This result confirmed that the DPDPE-induced dopamine release requires an initial glutamate release. However, this effect could reflect a major disruption of glutamatergic transmission caused by the toxin, as suggested by the local infusion of glutamine (2.5 mM) which, in lesioned rats, prevented the decrease in the basal extracellular content of glutamate and restored the DPDPE-induced increase in glutamate and dopamine dialysate levels. Therefore, these results indicate that, although glial cells are essential to maintain functional glutamatergic neurotransmission, they are not directly involved in the process by which stimulation of striatal δ-opioid receptors induces extracellular glutamate release and, consecutively, dopamine release.     

Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment)

The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.     

Amino acid degradation and effect of leucine on pyruvate oxidation in rat atrial muscle

Both left and right atria from fasted rats produced significant amounts of 14CO2 during incubation with U-14C-labeled leucine, isoleucine, valine, alanine, glutamate, glutamine, aspartate, asparagine, proline, threonine, or lysine. This pattern of amino acid metabolism resembles that of skeletal muscle. Production of 14CO2 from [1-14C]leucine was 2.5-fold greater in atria from fasted than from fed rats and was due to greater alpha-ketoisocaproic dehydrogenase activity in the tissue from fasted animals. At normal plasma concentrations, leucine reduced the oxidation of glucose and lactate in atria from fasted but not from fed rats by inhibiting pyruvate oxidation and without altering the rate of glycolysis. Leucine also reduced glucose oxidation when added in the presence of ketone bodies or other amino acids and stimulated the release of lactate into the medium. Although the leucine skeleton can be completely oxidized to CO2 and thus can serve as an alternative fuel in fasting in place of glucose, oxidation of leucine (like glucose or lactate oxidation) accounts only for a very small fraction of the total oxygen consumption of the resting atria.     

Glutamate-induced sensitization of rat masseter muscle fibers.

In rats, intradermal or intraarticular injection of glutamate or selective excitatory amino acid receptor agonists acting at peripheral excitatory amino acid receptors can decrease the intensity of mechanical stimulation required to evoke nocifensive behaviors, an indication of hyperalgesia. Since excitatory amino acid receptors have been found on the terminal ends of cutaneous primary afferent fibers, it has been suggested that increased tissue glutamate levels may have a direct sensitizing effect on primary afferent fibers, in particular skin nociceptors. However, less is known about the effects of glutamate on deep tissue afferent fibers. In the present study, a series of experiments were undertaken to investigate the effect of intramuscular injection of glutamate on the excitability and mechanical threshold of masseter muscle afferent fibers in anesthetized rats of both sexes.Injection of 1.0 M, but not 0.1 M glutamate evoked masseter muscle afferent activity that was significantly greater than that evoked by isotonic saline. The mechanical threshold of masseter muscle afferent fibers, which was assessed with a Von Frey hair, was reduced by approximately 50% for a period of 30 min after injection of 1.0 M glutamate, but was unaffected by injections of 0.1 M glutamate or isotonic saline. Injection of 25% dextrose, which has the same osmotic strength as 1.0 M glutamate, did not evoke significant activity in or decrease the mechanical threshold of masseter muscle afferent fibers. Magnetic resonance imaging experiments confirmed that injection of 25% dextrose and 1.0 M glutamate produced similar edema volumes in the masseter muscle tissue. Co-injection of 0.1 M kynurenate, an excitatory amino acid receptor antagonist, and 1.0 M glutamate attenuated glutamate-evoked afferent activity and prevented glutamate-induced mechanical sensitization. When male and female rats were compared, no difference in the baseline mechanical threshold or in the magnitude of glutamate-induced mechanical sensitization of masseter muscle afferent fibers was observed; however, the afferent fiber activity evoked by injection of 1.0 M glutamate into the masseter muscle was greater in female rats.The results of the present experiments show that intramuscular injection of 1.0 M glutamate excites and sensitizes rat masseter muscle afferent fibers through activation of peripheral excitatory amino acid receptors and that glutamate-evoked afferent fiber activity, but not sensitization, is greater in female than male rats.     

Consequences of prolonged total body immersion in cold water on muscle performance and EMG activity

The consequences of a prolonged total body immersion in cold water on the muscle function have not been documented yet, and they are the object of this French Navy research program. Ten elite divers were totally immerged and stayed immobile during 6 h in cold (18 and 10°C) water. We measured the maximal voluntary leg extension (maximal voluntary contraction, MVC) and evoked compound muscle potential (M wave) in vastus lateralis and soleus muscles at rest, after a submaximal (60% MVC) isometric extension allowing the measurement of the endurance time (Tlim). The power spectrum of surface electromyograms (EMG) was computed during 60% MVCs. MVCs and 60% MVC maneuvers were repeated four times during the immersion. Data were compared with those obtained in a control group studied in dry air condition during a 6-h session. Total body cooling did not affect MVC nor Tlim. The M wave duration increased in the coolest muscle (soleus), but only at 10°C at rest. There were no further fatigue-induced M wave alterations in both muscles. During 60% the MVCs, a time-dependant increase in the leftward shift of the EMG spectrum occurred at the two temperatures. These EMG changes were absent in the control group of subjects studied in dry air. The plasma lactate concentration was elevated throughout the 18 and mostly the 10°C immersion conditions. Throughout the 18°C immersion study, the resting potassium level did not significantly vary, whereas at 10°C, a significant potassium increase occurred soon and persisted throughout the study. Thus, total body immersion in cold water did not affect the global contractile properties of leg muscles during static efforts but elicited significant alterations in electromyographic events which may be related to the variations of interstitial fluid composition.     

High energy phosphates and related compounds,glycogen levels and histology in the rat tibialis anterior muscle after forced lengthening and isometric exercise

Eccentric exercise may elicit damage to the contractile elements. This primary damage is followed by secondary changes, consisting of histological changes and changes in glycogen and energy metabolism. The mechanism underlying changes in glycogen homeostasis and energy metabolism is not well established. The aim of this study was to investigate the possible relationship between changes in adenine and guanine nucleotides, inosine monophosphate (IMP), creatine phosphate, glycogen content and histology in the rat tibialis anterior (TA) muscle after forced lengthening or isometric exercise. The right muscles were either forcibly lenghtened or isometrically exercised, while the contralateral muscles served as non-exercised controls. The exercised muscles were dissected 0, 6 and 24 h post-exercise and the contents of adenine and guanine nucleotides, IMP, creatine phosphate, and glycogen determined. In addition, histological changes were assessed. Immediately after both types of exercise increases in tissue IMP levels were found. Irrespective of the type of exercise, glycogen content was decreased immediately post-exercise, but restored 6 h postexercise. Twenty-four hours later a second decline in glycogen content was found after both types of exercise. In forcibly lengthened muscles ATP content was decreased 24 h post-exercise. In isometrically exercised muscles ATP was not decreased at any time. Gross structural changes were found in all forcibly lengthened muscles (9–12% of TA muscle volume). In isometrically exercised muscles structural changes were minor (up to 0.1 % of muscle volume), were found only immediately post-exercise and in only 4 out of 18 muscles. It is concluded that forced lengthening results in decreased ATP levels. Changes in glycogen homeostasis were found after both isometric exercise and forced lengthening, demonstrating that these changes are not strictly related to degenerative changes.     

The rate of resting heat production of rat papillary muscle

The rate of resting heat production of quiescent rat left ventricular papillary muscles was measured myothermically. The effects of contractile activity, stretch, oxygen partial pressure, temperature, amino acids and time were examined. The rate of basal heat production was the same throughout the day whether or not muscles contracted isotonically under a small pre-load. Passive stretch increased the rate of resting heat production; the stretch-induced increment was highly variable from muscle to muscle. The resting heat rate per se was only moderately sensitive to oxygen partial pressure and temperature, and was insensitive to the presence of amino acids in the bathing medium. The stretch-induced increase in resting heat rate was independent of these three factors. The rate of resting heat production declined exponentially with time to reach a plateau about 4 h following cardiectomy.     

Absence of humoral mediated 5'AMP-activated protein kinase activation in human skeletal muscle and adipose tissue during exercise

5'AMP-activated protein kinase (AMPK) exists as a heterotrimer comprising a catalytic α subunit and regulatory β and γ subunits. The AMPK system is activated under conditions of cellular stress, indicated by an increase in the AMP/ATP ratio, as observed, e.g. in muscles during contractile activity. AMPK was originally thought to be activated only by local intracellular mechanisms. However, recently it has become apparent that AMPK in mammals is also regulated by humoral substances, e.g. catecholamines. We studied whether humoral factors released during exercise regulate AMPK activity in contracting and resting muscles as well as in abdominal subcutaneous adipose tissue in humans. In resting leg muscle and adipose tissue the AMPK activity was not up-regulated by humoral factors during one-legged knee extensor exercise even when arm cranking exercise, inducing a ∼20-fold increase in plasma catecholamine level, was added simultaneously. In exercising leg muscle the AMPK activity was increased by one-legged knee extensor exercise eliciting a whole body respiratory load of only 30%     but was not further increased by adding arm cranking exercise. In conclusion, during exercise with combined leg kicking and arm cranking, the AMPK activity in human skeletal muscle is restricted to contracting muscle without influence of marked increased catecholamine levels. Also, with this type of exercise the catecholamines or other humoral factors do not seem to be physiological regulators of AMPK in the subcutaneous adipose tissue.     

Fluid balance in exercise dehydration and rehydration with different glucose-electrolyte drinks

Summary After exercise dehydration (3% of body weight) the restoration of water and electrolyte balance was followed in 6 male subjects. During a 2 h rest period after exercise, a drink of one of four solutions was given as 9×300 ml portions at 15 min intervals: control (C-drink), high potassium (K-drink), high sodium (Na-drink) or high sugar (S-drink). An exercise test (submaximal and supramaximal work) was performed before dehydration and after rehydration. Dehydration reduced plasma volume by 16%, a process reversed on resting even before fluid ingestion began, due to release of water accumulated in the muscles during exercise. After 2 h rehydration, plasma volume was above the initial resting value with all 4 drinks. The final plasma volumes after the Na-drink (+14%) and C-drink (+9%) were significantly higher than after the K- and S-drinks. The Na-drink favoured filling of the extracellular compartment, whereas the K- and S-drinks favoured intracellular rehydration. In spite of the higher than normal plasma volume after rehydration, mean heart rate during the submaximal test was 10 bpm higher after rest and rehydration than in the initial test, and was not different between the drinks. The amount of work which could be performed in the supramaximal test (105% ) was 20% less after exercise dehydration and subsequent rest and rehydration than before. This reduction was similar for all drinks, and may be due to a decreased muscle glycogen content (70% of initial) at the time of the second test. Danish National Institute of Occupational Health     

Functions of adrenergic and cholinergic nerves in canine effectors of seminal emission

Spontaneous activity responses to acetylcholine (ACh), adrenaline (A), noradrenaline (NA) and barium chloride as well as the effects of various autonomic drugs on effects of field stimulation of nerves and muscle cells of isolated pieces or strips of cauda epididymidis, vas deferens, ampulla ductus deferentis and prostate of dog were studied. The main results and conclusions are: the muscles show little spontaneous activity but rhythmicity can easily be produced by e.g. stimulating agonists. The muscles are contracted by alpha-adrenoceptor stimulants. ACh has usually no or a very weak contractile effect in high concentrations. Muscles of young dogs are more sensitive to ACh. The excitatory innervation of the muscles is adrenergic and completely blocked by adrenergic neuron blockers as well as alpha-adrenoceptor blocking drugs. Stimulation of adrenergic nerves leads to maximum response already at low frequencies (4-6 Hz). This response is very similar to that provoked by a supramaximal dose of NA. Scopolamine enhances neurogenic contractile effects while physostigmine suppresses them. Hence cholinergic nerves may act by muscarinic prejunctional inhibition of the excitatory adrenergic neurotransmission rather than act directly upon the smooth muscle cells. Since secretory cells receive cholinergic innervation prejunctional inhibition of the adrenergic myomotor nerves may be of functional significance in at least the long copulatory events of the dog.     

Physiological and biochemical characteristics of skeletal muscles in sedentary and active rats

Laboratory rats are sedentary if housed in conditions where activity is limited. Changes in muscle characteristics with chronic inactivity were investigated by comparing sedentary rats with rats undertaking voluntary wheel running for either 6 or 12 weeks. EDL (type II fibers) and soleus (SOL) muscles (predominantly type I fibers) were examined. When measured within 1–2 h post-running, calcium sensitivity of the contractile apparatus was increased, but only in type II fibers. This increase disappeared when fibers were treated with DTT, indicative of oxidative regulation of the contractile apparatus, and was absent in fibers from rats that had ceased running 24 h prior to experiments. Specific force production was ~?10 to 25% lower in muscle fibers of sedentary compared to active rats, and excitability of skinned fibers was decreased. Muscle glycogen content was ~?30% lower and glycogen synthase content?~?50% higher in SOL of sedentary rats, and in EDL glycogenin was 30% lower. Na⁺, K⁺-ATPase α1 subunit density was ~?20% lower in both EDL and SOL in sedentary rats, and GAPDH content in SOL?~?35% higher. There were no changes in content of the calcium handling proteins calsequestrin and SERCA, but the content of CSQ-like protein was increased in active rats (by ~?20% in EDL and 60% in SOL). These findings show that voluntary exercise elicits an acute oxidation-induced increase in Ca²⁺ sensitivity in type II fibers, and also that there are substantial changes in skeletal muscle characteristics and biochemical processes in sedentary rats.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

The effect of dynamic exercise on muscle and blood ammonia (NH3) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5.2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH3 at rest and after submaximal exercise was (means +/- SE) 0.5 +/- 0.1 mmol/kg dry muscle (d.m.) and increased to 4.1 +/- 0.5 mmol/kg d.m. at fatigue (P less than 0.001). The total adenine nucleotide (TAN) pool (TAN = ATP + ADP + AMP) did not change after submaximal exercise but decreased significantly at fatigue (P less than 0.001). The decrease in TAN was similar to the increase in NH3. Muscle lactate was 3 +/- 1 mmol/kg d.m. at rest and increased to 104 +/- 5 mmol/kg d.m. at fatigue. Whole blood and plasma NH3 did not change significantly during submaximal but both increased significantly during maximal exercise (P less than 0.001). During maximal exercise the leg released 7,120 mumol/min of lactate, whereas only 89 mumol/min of NH3 were released. NH3 accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH3 release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P less than 0.001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P less than 0.001), respectively, during exercise. It is concluded that (1) muscle and blood NH3 levels increase only during strenuous exercise and (2) NH3 accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Skeletal muscle and hormonal adaptation to physical training in the rat: role of the sympatho-adrenal system

The main purpose of the present study was to test the hypothesis that adrenergic stimulation of muscle fibres during exercise is a major stimulus for the training-induced enhancement of skeletal muscle respiratory capacity. Therefore, Sprague-Dawley rats either underwent bilateral surgical ablation of the adrenal medulla or were sham-operated. Furthermore, unilateral surgical extirpation of the lumbar sympathetic chain was performed. Half of the rats were then trained for 12 weeks by swimming (up to 5.5 h X day-1, 4 days X week-1) and the remaining rats were sedentary controls. In the gastrocnemius muscle, training significantly increased the mitochondrial enzymes citrate synthase, succinate dehydrogenase, cytochrome c oxidase, and 3-hydroxyacyl-CoA dehydrogenase. In sham-operated rats, the increases were 40%, 43%, 66%, and 25%, respectively, in legs with intact sympathetic innervation. The training-induced enzyme adaptation after adrenodemedullation and/or sympathectomy was not significantly lower than these control values. In sham-operated rats, training decreased resting plasma insulin and glucagon levels and increased liver glycogen content. Similar changes were induced by adrenodemedullation, but training did not augment these changes in adrenodemedullated rats. In conclusion, the data suggest that neither adrenomedullary hormones nor local sympathetic nerves are prerequisites for the training-induced increase in muscle mitochondrial enzymes. The training-induced decline in resting plasma insulin and glucagon levels in intact rats may be mediated by adrenomedullary hormones.