Fast-twitch skeletal muscle fiber adaptation to SERCA1 deficiency in a Dutch Improved Red and White calf pseudomyotonia case.

Missense mutations in ATP2A1 gene, encoding SERCA1 protein, cause a muscle disorder designed as congenital pseudomyotonia (PMT) in Chianina and Romagnola cattle or congenital muscular dystonia1 (CMD1) in Belgian Blue cattle. Although PMT is not life-threatening, CMD1 affected calves usually die within a few weeks of age as a result of respiratory complication. We have recently described a muscular disorder in a double muscle Dutch Improved Red and White cross-breed calf. Mutation analysis revealed an ATP2A1 mutation identical to that described in CMD1, even though clinical phenotype was quite similar to that of PMT. Here, we provide evidence for a deficiency of mutated SERCA1 in PMT affected muscles of Dutch Improved Red and White calf, but not of its mRNA. The reduced expression of SERCA1 is selective and not compensated by the SERCA2 isoform. By contrast, pathological muscles are characterized by a broad distribution of mitochondrial markers in all fiber types, not related to intrinsic features of double muscle phenotype and by an increased expression of sarcolemmal calcium extrusion pump. Calcium removal mechanisms, operating in muscle fibers as compensatory response aimed at lowering excessive cytoplasmic calcium concentration caused by SERCA1 deficiency, could explain the difference in severity of clinical signs.

ADAPTATION OF INTESTINAL MUSCLE IN THE RAT AFTER INTESTINAL BYPASS

After intestinal bypass, the mucosa of the in-continuity segment (ICS) of intestine undergoes adaptive hyperplasia which results in increased absorptive function per length of intestine. In the present study, 70% of the small intestine was bypassed in rats to determine if intestinal muscle also adapts after bypass. To determine the effect of bypass on intestinal transit, a poorly absorbed marker substance was introduced into the orad portion of the ICS or bypassed loop (BL). Significantly less marker (P < 0.05) was passed from the ICS into the colon in 50 minutes in fed rats at 14 days compared to at 3 days after bypass. In 150 minutes there was more marker in the colon of fed rats at 3 and 14 days but not at 35 days after bypass than in control. In the BL, transit was slowed significantly in fed rats at 3 and 35 days and in fasted rats at 3 days but not 35 days after bypass compared to control. The circular muscle from the BL and the distal but not proximal portion of the ICS developed significantly more carbachol-stimulated force in vitro at 35 but not 3 days after bypass compared to unoperated but not sham-operated controls. At 35 days after bypass, the muscle layers had a greater muscle wet weight and protein content compared to both unoperated and sham-operated control in both the proximal and distal portions of the ICS. Similarly, there was more muscle in histological sections of the BL and distal portion of the ICS at 35 days after bypass compared to either control. Nonetheless, at 35 days after bypass actomyosin content as a fraction of muscle weight or total protein content was not different from control. The results support the hypothesis that there was a functional adaptation, i.e. slowed transit in fed rats that allowed more time for absorption. Feeding caused slowed transit in the BL as well as the ICS. Other results suggest that an increased amount of functional muscle formed in the distal portion of the ICS after bypass. ^

Adaptation and maladaptation of heart and skeletal muscle to different diets in a rodent model of human obesity

Obesity and diabetes are metabolic disorders associated with fatty acid availability in excess of the tissues' capacity for fatty acid oxidation. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in skeletal muscle insulin resistance. My dissertation will present work to test the overall hypothesis that "western" and high fat diets differentially affect cardiac and skeletal muscle fatty acid oxidation, the expression of fatty acid responsive genes, and cardiac contractile function. Wistar rats were fed a low fat, "western," or high fat (10%, 45%, or 60% calories from fat, respectively) diet for acute (1 day to 1 week), short (4 to 8 weeks), intermediate (16 to 24 weeks), or long (32 to 48 weeks) term. With high fat diet, cardiac oleate oxidation increased at all time points investigated. In contrast, with western diet cardiac oleate oxidation increased in the acute, short and intermediate term, but not in the long term. Consistent with a maladaptation of fatty acid oxidation, cardiac power (measured ex vivo) decreased with long term western diet only. In contrast to the heart, soleus muscle oleate oxidation increased only in the acute and short term with either western or high fat feeding. Transcript analysis revealed that several fatty acid responsive genes, including pyruvate dehydrogenase kinase 4, uncoupling protein 3, mitochondrial thioesterase 1, and cytosolic thioesterase 1 increased in heart and soleus muscle to a greater extent with high fat diet, versus western diet, feeding. In conclusion, the data implicate inadequate induction of a cassette of fatty acid responsive genes in both the heart and skeletal muscle by western diet resulting in impaired activation of fatty acid oxidation, and the development of cardiac dysfunction. ^

Adaptation of motor control to training and disuse : contribution of muscle synergy analysis and movement variability

The well-known degrees of freedom problem originally introduced by Nikolai Bernstein (1967) results from the high abundance of degrees of freedom in the musculoskeletal system. Such abundance in motor control have two sides: i) because it is unlikely that the Central Nervous System controls each degree of freedom independently, the complexity of the control needs to be reduced, and ii) because there are many options to perform a movement, a repetition of a given movement is never the same. It leads to two main topics in motor control and biomechanics: motor coordination and motor variability. The present thesis aimed to understand how motor systems behave and adapt under specific conditions. This thesis comprises three studies that focused on three topics of major interest in the field of sports sciences and medicine: expertise, injury risk and fatigue. The first study (expertise) has focused on the muscle coordination topic to further investigate the effect of expertise on the muscle synergistic organization, which ultimately may represent the underlying neural strategies. Studies 2 (excessive medial knee displacement) and 3 (fatigue) both aimed to better understand its impact on the dynamic local stability. The main findings of the present thesis suggest: 1) there is a great robustness in muscle synergistic organization between swimmers at different levels of expertise (study 1, chapter II), which ultimately indicate that differences in muscle coordination is mainly explained by peripheral adaptations; 2) injury risk factors such as excessive medial knee displacement (study 2, chapter III) and fatigue (study 3, chapter IV) alter the dynamic local stability of the neuromuscular system towards a more unstable state. This change in dynamic local stability represents a loss of adaptability in the neuromuscular system reducing the flexibility to adapt to a perturbation.

Effect of eccentric contraction velocity on muscle damage in repeated bouts of elbow flexor exercise

Eccentric exercise induces muscle damage, but controversy exists concerning the effect of contraction velocity on the magnitude of muscle damage, and little is known about the effect of contraction velocity on the repeated-bout effect. This study examined slow (60 degrees.s(-1)) and fast (180 degrees.s(-1)) velocity eccentric exercises for changes in indirect markers of muscle damage following 3 exercise bouts that were performed every 2 weeks. Fifteen young men were divided into 2 groups based on the velocity of eccentric exercise: 7 in the Ecc60 (60 degrees.s(-1)) group, and 8 in the Ecc180 (180 degrees.s(-1)) group. The exercise consisted of 30 maximal eccentric contractions of the elbow flexors at each velocity, in which the elbow joint was forcibly extended from 60 degrees to 180 degrees (full extension) on an isokinetic dynamometer. Changes in maximal voluntary isometric contraction strength, range of motion, muscle soreness, and plasma creatine kinase activity before and for 4 days after the exercise were compared in the 2 groups using a mixed-model analysis (group x bout x time). No significant differences between groups were evident for changes in any variables following exercise bouts; however, the changes were significantly smaller (p < 0.05) after the second and third bouts than after the first bout. These results indicate that the contraction velocity does not influence muscle damage or the repeated-bout effect.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training

SILVA, B. M., F. J. NEVES, M. V. NEGRÃO, C. R. ALVES, R. G. DIAS, G. B. ALVES, A. C. PEREIRA, M. Urbana A. RONDON, J. E. KRIEGER, C. E. NEGRÃO, and A. C. DA NOBREGA. Endothelial Nitric Oxide Synthase Polymorphisms and Adaptation of Parasympathetic Modulation to Exercise Training. Med. Sci. Sports Exerc., Vol. 43, No. 9, pp. 1611-1618, 2011. Purpose: There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. Methods: Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption ((V) over dotO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min.day(-1), during 18 wk). Results: Training increased (V) over dotO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% +/- 89% vs polymorphic (-786TC/CC) = -28% +/- 60%, median +/- quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% +/- 67% vs polymorphic (894GT/TT) = -18% +/- 59%, median +/- quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles(-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% +/- 56% vs -41% +/- 50%, median T quartile range, P = 0.04). Conclusions: The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.

The sites of neural adaptation induced by resistance training in humans

Although it has long been supposed that resistance training causes adaptive changes in the CNS, the sites and nature of these adaptations have not previously been identified. In order to determine whether the neural adaptations to resistance training occur to a greater extent at cortical or subcortical sites in the CNS, we compared the effects of resistance training on the electromyographic (EMG) responses to transcranial magnetic (TMS) and electrical (TES) stimulation. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle of 16 individuals before and after 4 weeks of resistance training for the index finger abductors (n = 8), or training involving finger abduction-adduction without external resistance (n = 8). TMS was delivered at rest at intensities from 5 % below the passive threshold to the maximal output of the stimulator. TMS and TES were also delivered at the active threshold intensity while the participants exerted torques ranging from 5 to 60 % of their maximum voluntary contraction (MVC) torque. The average latency of MEPs elicited by TES was significantly shorter than that of TMS MEPs (TES latency = 21.5 ± 1.4 ms; TMS latency = 23.4 ± 1.4 ms; P < 0.05), which indicates that the site of activation differed between the two forms of stimulation. Training resulted in a significant increase in MVC torque for the resistance-training group, but not the control group. There were no statistically significant changes in the corticospinal properties measured at rest for either group. For the active trials involving both TMS and TES, however, the slope of the relationship between MEP size and the torque exerted was significantly lower after training for the resistance-training group (P < 0.05). Thus, for a specific level of muscle activity, the magnitude of the EMG responses to both forms of transcranial stimulation were smaller following resistance training. These results suggest that resistance training changes the functional properties of spinal cord circuitry in humans, but does not substantially affect the organisation of the motor cortex.

Muscle fibre types and size distribution in sub-antarctic notothenioid fishes

The presumptive tonic muscles fibres of Cottoperca gobio, Champsocephalus esox, Harpagifer bispinis, Eleginops maclovinus, Patagonothen tessellata, P. cornucola and Paranotothenia magellanica stained weakly or were unstained for glycogen, lipid, succinic dehydrogenase (SDHase) and myosin ATPase (mATPase) activity. Slow, intermediate and fast twitch muscle fibres, distinguished on the basis of the pH stability of their mATPases, showed intense, moderate and low staining activity for SDHase, respectively. Slow fibres were the major component of the pectoral fin adductor profundis muscle. The proportion of different muscle fibre types varied from the proximal to distal end of the muscle, but showed relatively little variation between species. The myotomes contained a lateral superficial strip of red muscle composed of presumptive tonic, slow twitch and intermediate fibres, thickening to a major wedge at the horizontal septum. All species also had characteristic secondary dorsal and ventral wedges of red muscle. The relative abundance and localization of muscle fibre types in the red muscle varied between species and with body size in the protandric hermaphrodite E. maclovinus. The frequency distribution of diameters for fast twitch muscle fibres, the major component of deep white muscle, was determined in fish of a range of body sizes. The absence of fibres <20 mu m diameter was used as a criterion for the cessation of muscle fibre recruitment. Fibre recruitment had stopped in P, tessellata of 13.8 cm L-T and E, maclovinus of 32.8 cm L-T, equivalent to 49 and 36.5% of their recorded maximum sizes respectively. As a result in 20-cm P. tessellata, the maximum fibre diameter was 300 mu m and 36% of fibres were in excess of 200 mu m The unusually large maximum fibre diameter, the general arrangement of the red muscle layer and the extreme pH lability of the mATPase of fast twitch fibres are all common characters of the sub-Antarctic and Antarctic Notothenioids, including Cottoperca gobio, the suggested sister group to the Notothenidae. (C) 2000 The Fisheries Society of the British Isles.

Intracellular free Ca2+ and basal Mn2+ influx in cultured aortic smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Numerous studies investigating the possible role of altered Ca2+ homeostasis in hypertension have compared resting and agonist-stimulated intracellular free Ca2+ ([Ca2+](i)) in cultured aortic smooth muscle cells from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. However, such studies have not given consistent results. Differences in the method used to load cells with the Ca2+-sensitive indicator fura-2 have been investigated here as a possible source of variability between studies. We also describe the adaptation of a fluorescence technique for the assessment of basal Ca2+ permeability in SHR and WKY through the measurement of Mn2+ influx. The results are consistent with the hypothesis that basal Ca2+ influx is elevated in cultured aortic smooth muscle cells from SHR compared to those from WKY. However, this was not reflected as a significant difference between the two strains in basal or angiotensin II (200 nmol/L)stimulated [Ca2+](i). Furthermore, this result was not dependent on the protocol used to load cells with fura-2. Hence, measurement of bulk [Ca2+](i) does not appear to be the most sensitive parameter for altered Ca2+ homeostasis in SHR. Other compartments of the cell may better reflect altered Ca2+ fluxes in hypertension and are discussed in this work.

Changes in postnatal skeletal muscle development induced by alternative immobilization model in female rat

The objective of this study was to adapt a model of hind limb immobilization to newly weaned female rats and to determine the morphology of shortened soleus and plantaris muscles. Female Wistar rats were divided into three groups: control zero (n = 3) and control and free (n = 8), animals aged 21 and 31 days, respectively, submitted to no intervention, and immobilized (n = 25), animals aged 21 days submitted to immobilization for 10 days and sacrificed at 31 days of age. The device used for immobilization had advantages such as easy connection, good fit, and low cost. The immobilized rats showed a reduction in muscle fiber area and in connective tissue. The adaptation of this immobilization model originally used for adult rats was an excellent alternative for newly weaned rats and was also efficient in inducing significant hind limb disuse.

Short-term beta-hydroxy-beta-methylbutyrate supplementation does not reduce symptoms of eccentric muscle damage

Purpose: We examined the effects of short-term beta -hydroxy-beta -methylbutyrate (HIM) supplementation on symptoms of muscle damage following an acute bout of eccentric exercise. Methods: Non-resistance trained subjects were randomly assigned to a HMB supplement group (HMB, 40mg/kg bodyweight/day, n = 8) or placebo group (CON, n = 9). Supplementation commenced 6 days prior to a bout of 24 maximal isokinetic eccentric contractions of the elbow flexors and continued throughout post-testing. Muscle soreness, upper arm girth, and torque measures were assessed pre-exercise, 15 min post-exercise, and 1, 2, 3, 4, 7, and 10 days post-exercise. Results: No pre-test differences between HMB and CON groups were identified, and both performed a similar amount of eccentric work during the main eccentric exercise bout (p > .05). HMB supplementation had no effect on swelling, muscle soreness, or torque following the damaging eccentric exercise bout (p > .05). Conclusion: Compared to a placebo condition, short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage. If HMB can produce an ergogenic response, a longer pre-exercise supplementation period may be necessary.

Adaptation to chronic eccentric exercise in humans: the influence of contraction velocity

We compared changes in muscle fibre composition and muscle strength indices following a 10 week isokinetic resistance training programme consisting of fast (3.14 rad(.)s(-1)) or slow (0.52 rad(.)s(-1)) velocity eccentric muscle contractions. A group of 20 non-resistance trained subjects were assigned to a FAST (n = 7), SLOW (n = 6) or non-training CONTROL (n = 7) group. A unilateral training protocol targeted the elbow flexor muscle group and consisted of 24 maximal eccentric isokinetic contractions (four sets of six repetitions) performed three times a week for 10 weeks. Muscle biopsy samples were obtained from the belly of the biceps brachii. Isometric torque and concentric and eccentric torque at 0.52 and 3.14 rad(.)s(-1) were examined at 0, 5 and 10 weeks. After 10 weeks, the FAST group demonstrated significant [mean (SEM)] increases in eccentric [29.6 (6.4)%] and concentric torque [27.4 (7.3) %] at 3.14 rad(.)s(-1), isometric torque [21.3 (4.3)%] and eccentric torque [25.2 (7.2) %] at 0.52 rad(.)s(-1). The percentage of type I fibres in the FAST group decreased from [53.8 (6.6)% to 39.1 (4.4)%] while type lib fibre percentage increased from [5.8 (1.9)% to 12.9 (3.3)%; P < 0.05]. In contrast. the SLOW group did not experience significant changes in muscle fibre type or muscle torque. We conclude that neuromuscular adaptations to eccentric training stimuli may be influenced by differences in the ability to cope with chronic exposure to relatively fast and slow eccentric contraction velocities. Possible mechanisms include greater cumulative damage to contractile tissues or stress induced by slow eccentric muscle contractions.