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Acute mountain sickness (AMS) occurs due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but inhibits exercise performance. Methazolamide (MZ), an analogous drug, has similar prophylactic benefits but does not impair isolated muscle mass exercise performance in normoxia. We sought to compare whole body exercise performance in acute hypoxia (fraction of inspired oxygen, F I O 2 = 0.15) between AZ, MZ, and placebo (PLA). Fifteen healthy participants completed five testing visits: day 1 for maximal exercise test, day 2 for familiarization, and days 3–5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial (TT) performed after a 2-day dosing protocol of either AZ (250 mg three times a day), MZ (100 mg twice a day), or PLA (three times a day); the order was randomized and double-blinded. Before exercise, capillary blood samples were taken, and maximal voluntary contractions of quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest compared with PLA [capillary hydrogen ions (H+) 47 ± 3, 43 ± 2, and 39 ± 2 nmol for AZ, MZ, and PLA respectively, P < 0.01]. Time to complete 5 km with PLA (562 ± 32 s, P < 0.01) was significantly faster than AZ and MZ (577 ± 38 vs. 581 ± 37 s, respectively), with no differences between AZ and MZ (P = 0.96). There were no differences in average ventilation (124 ± 27, 127 ± 24, 127 ± 19 L/min) and oxyhemoglobin saturation (87 ± 2, 88 ± 2, 88 ± 3%) between AZ, MZ, and PLA, respectively (P > 0.05). Overall, both AZ and MZ impair whole body exercise performance in acute normobaric hypoxia. NEW & NOTEWORTHY: Administration of acetazolamide (AZ) and methazolamide (MZ) both resulted in a significantly slower 5-km time trial in acute normobaric hypoxia compared with a placebo. Both drugs lead to a partially compensated metabolic acidosis, but ventilation and oxyhemoglobin saturation were not different across the conditions. Overall, acetazolamide and methazolamide both impaired whole body exercise performance in acute normobaric hypoxia but potentially have different mechanisms of action. [ABSTRACT FROM AUTHOR]

The amount of calcium released from the sarcoplasmic reticulum in skeletal muscle rapidly declines during repeated twitch contractions. In this study, we test the hypothesis that caffeine can mitigate these contraction-induced declines in calcium release. Lumbrical muscles were isolated from male C57BL/6 mice and loaded with the calcium-sensitive indicator, AM-furaptra. Muscles were then stimulated at 8 Hz for 2.0 s in the presence or absence of 0.5 mM caffeine, at either 30 [degrees]C or 37 [degrees]C. The amplitude and area of the furaptra-based intracellular calcium transients and force produced during twitch contractions were calculated. For each of these measures, the values for twitch 16 relative to twitch 1 were higher in the presence of caffeine than in the absence of caffeine at both temperatures. We conclude that caffeine can attenuate contraction-induced diminutions of calcium release during repeated twitch contractions, thereby contributing to the inotropic effects of caffeine. Key words: skeletal muscle, calcium-sensitive indicators, AM-furaptra, staircase, force potentiation, twitch. La quantite de calcium libere du reticulum sarcoplasmique du muscle squelettique diminue rapidement pendant des saccades de contractions repetees. Dans cette etude, nous tentons de verifier l'hypothese selon laquelle la cafeine peut attenuer ces diminutions de liberation de calcium engendrees par les contractions. Nous avons isole des muscles interosseux de souris C57BL/6 males et nous les avons charges d'AM-furaptra, un indicateur sensible au calcium. Nous avons ensuite stimule les muscles a 8 Hz pendant 2,0 s en presence ou en absence de cafeine a 0,5 mM, a 30 ou a 37 [degrees]C. Nous avons calcule la force developpee, ainsi que l'amplitude et la surface sous la courbe des courants intracellulaires de calcium transitoires obtenue a l'aide de furaptra pendant les saccades de contraction. Pour chacune de ces mesures, les valeurs etaient plus elevees pour la saccade 16 que pour la saccade 1 en presence de cafeine qu'en absence de cafeine, et ce, aux deux temperatures. Nous en arrivons a la conclusion que la cafeine peut entrainer une attenuation des diminutions de liberation de calcium engendrees par les contractions pendant des saccades de contraction repetees, ce qui contribuerait aux effets inotropes de la cafeine. [Traduit par la Redaction] Mots-cles: muscle squelettique, indicateurs sensibles au calcium, AM-furaptra, escalier, potentialisation de la force, saccade., Introduction The rise and fall of free myoplasmic [Ca.sup.2+] levels following a single depolarization is collectively termed the intracellular [Ca.sup.2+] transient (ICT) (Calderon et al. 2014). The amount of [Ca.sup.2+] [...]

This study assessed neuromuscular function in the extensor carpi radialis brevis (ECRB) of female workers diagnosed with work-related myalgia (WRM, n = 14, age 45.2 [+ or -] 1.9 years) and the ECRB of healthy controls (CON, n = 10, age 34.6 [+ or -] 2.5 years). Groups were compared on voluntary and electrically evoked functional responses at rest (Pre), immediately following a 5 min repetitive task (Post-0) performed at 60% maximal voluntary contraction (MVC), and after 5 min of recovery (Post-5). Despite near complete motor unit activation (MUA) (CON 98% [+ or -] 1% vs. WRM 99% [+ or -] 1%), at Pre, WRM produced 26% less (P 0.05) between groups and MUA was not impaired (CON 97% [+ or -] 1% vs. WRM 97% [+ or -] 1%; P > 0.05). In conclusion, the peripheral weakness observed in the ECRB in WRM at rest does not result in abnormal fatigue or recovery responses after performing a task controlled for relative demand (60% MVC). Key words: myalgia, work, extensor carpi radialis brevis, neuromuscular, fatigue, women. Cette etude portait sur la fonction neuromusculaire dans le muscle court extenseur radial du carpe (CERC) de travailleuses ayant recu un diagnostic de myalgie liee au travail (MLT, n = 14, age de 45,2 [+ or -] 1,9 ans) et dans le muscle CERC de temoins en bonne sante (TEM, n = 10, age de 34,6 [+ or -] 2,5 ans). Nous avons compare entre les groupes les reactions fonctionnelles evoquees volontairement et electriquement au repos (Pre), immediatement apres l'accomplissement d'une tache repetitive effectuee a 60% de la contraction volontaire maximale (CVM) pendant 5 min (Post-0) et apres une recuperation de 5 min (Post-5). Meme si l'activation des unites motrices (AUM) etait presque complete (TEM 98 [+ or -] 1% vs. MLT 99 [+ or -] 1%) au temps Pre, la force de CVM etait 26% plus faible dans le groupe MLT que dans le groupe TEM (P < 0,05). A la suite de la CVM, la force stimulee augmentait (P < 0,05) de 94 [+ or -] 13 et de 54 [+ or -] 11% dans les groupes TEM et MLT, respectivement (comparaison entre les groupes : P < 0,05). La force maximale ainsi que les vitesses maximales de developpement de la force et de declin des contractions stimulees electriquement (10 a 100 Hz) etaient generalement diminuees (P < 0,05) aux temps Post-0 et Post-5 par rapport au temps Pre. Le schema des reactions a la stimulation a des frequences croissantes n'etait pas different (P > 0,05) entre les groupes, et l'AUM n'etait pas compromise (TEM 97 [+ or -] 1% vs. MLT 97 [+ or -] 1%; P > 0,05). En conclusion, la faiblesse des membres observee dans le muscle CERC au repos en cas de MLT n'est pas le fait d'une fatigue ni d'une reaction de recuperation anormales apres avoir effectue une tache avec demande relative controlee (a 60% de la CVM). [Traduit par la Redaction] Mots-cles : myalgie, travail, court extenseur radial du carpe, neuromusculaire, fatigue, femmes., Introduction It is widely acknowledged that the diagnosis and, consequently, the prevention and treatment of work related myalgia (WRM) is confounded by the lack of accepted objective clinical landmarks (Gerdle [...]

In this study, we sought to determine whether differences in cellular properties associated with energy homeostasis could explain the higher incidence of work-related myalgia in trapezius (TRAP) compared with extensor carpi radialis brevis (ECRB). Tissue samples were obtained from the ECRB (n = 19) and TRAP (n = 17) of healthy males and females (age 27.9 [+ or -] 2.2 and 28.1 ± 1.5 years, respectively; mean ± SE) and analyzed for properties involved in both ATP supply and utilization. The concentration of ATP and the maximal activities of creatine phosphokinase, phosphorylase, and phosphofructokinase were higher (P < 0.05) in ECRB than TRAP. Succinic dehydrogenase, citrate synthase, and cytochrome c oxidase were not different between muscles. The ECRB also displayed a higher concentration of [Na.sup.+]-[K.sup.+]-ATPase and greater sarcoplasmic reticulum [Ca.sup.2+] release and uptake. No differences existed between muscles for either monocarboxylate transporters or glucose transporters. It is concluded that the potentials for high-energy phosphate transfer, glycogenolysis, glycolysis, and excitation-contraction coupling are higher in ECRB than TRAP. Histochemical measurements indicated that the muscle differences are, in part, related to differing amounts of type II tissue. Depending on the task demands, the TRAP may experience a greater metabolic and excitationcontraction coupling strain than the ECRB given the differences observed. Key words: excitation-contraction coupling, fibre type distribution, metabolic pathways, substrates, transporters. Cette etude avait pour objectif de determiner si des proprietes dissemblables de l'homeostasie cellulaire pourraient expliquer l'augmentation de la frequence de myalgies associees a l'effort dans l'extenseur radial du carpe (ERC) comparativement au trapeze (TPZ). Nous avons etudie les proprietes liees a l'approvisionnement en ATP et a son utilisation dans des echantillons de tissu d'ERC (n = 19) et de TPZ (n = 17) preleves chez des hommes et des femmes en bonne sante (ages de 27,9 ± 2,2 et de 28,1 ± 1,5 ans [moyenne ± ET], respectivement). La concentration d'ATP et les activites maximales de la creatine phosphokinase, de la phosphorylase et de la hosphofructokinase etaient plus elevees (P < 0,05) dans l'ERC que dans le TPZ, alors que celles de la deshydrogenase succinique, de la citrate synthase et de la cytochrome c oxydase etaient semblables dans les deux types de muscle. En outre, les concentrations de [Na.sup.+]-[K.sup.+]-ATPase ainsi que les taux de liberation et de recapture de l'ion [Ca.sup.2+] etaient plus eleves dans le reticulum sarcoplasmique de l'ERC que dans celui du TPZ, alors que les caracteristiques des transporteurs de monocarboxylates et des transporteurs du glucose etaient semblables dans les deux types de muscle. Nous en arrivons a la conclusion que les potentiels de transfert de phosphates riches en energie, de glycogenolyse, de glycolyse et de couplage excitation-contraction sont plus eleves dans l'ERC que dans le TPZ. Les mesures histochimiques indiquent que ces differences entre les 2 types de muscle sont, en partie, liees aux disparites entre les quantites de tissu de type II. Etant donne les differences observees, des contraintes plus importantes pourraient etre imposees au TPZ qu'a l'ERC sur le plan metabolique et du couplage excitation-contraction selon les exigences des taches. [Traduit par la Redaction] Mots-cles: couplage excitation-contraction, distribution des types de fibre, voies metaboliques, substrats, transporteurs., Introduction Two major observations continue to perplex clinicians and scientists involved in contractile-related disorders to the upper extremity such as work-related myalgia (WRM). Of concern is the underlying bases for [...]

This study compared both the extensor carpi radialis brevis (ECRB) and the trapezius (TRAP) muscles of women with work-related myalgia (WRM) with healthy controls (CON) to determine whether abnormalities existed in cellular energy status and the potentials of the various metabolic pathways and segments involved in energy production and substrate transport. For both the ECRB (CON, n = 6-9; WRM, n = 13) and the TRAP (CON, n = 6-7; WRM, n = 10), no differences (P > 0.05) were found for the concentrations (in millimoles per kilogram of dry mass) of ATP, PCr, lactate, and glycogen. Similarly, with one exception, the maximal activities (in moles per milligram of protein per hour) of mitochondrial enzymes representative of the citric acid cycle (CAC), the electron transport chain (ETC), and [beta]-oxidation, as well as the cytosolic enzymes involved in high energy phosphate transfer, glycogenolysis, glycolysis, lactate oxidation, and glucose phosphorylation were not different (P > 0.05). The glucose transporters GLUT1 and GLUT4, and the monocarboxylate transporters MCT1 and MCT4, were also normal in WRM. It is concluded that, in general, abnormalities in the resting energy and substrate state, the potential of the different metabolic pathways and segments, as well as the glucose and monocarboxylate transporters do not appear to be involved in the cellular pathophysiology of WRM. Key words: energy potential, glucose transporters, monocarboxylate transporters, skeletal muscle, repetitive strain injury. Cette etude a compare le muscle court extenseur radial du carpe (CERC) et le trapeze (TRAP) de femmes affectee d'une myalgie professionnelle (MP) et de controles sains (CON) afin de determiner s'il existait des anomalies sur le plan de l'etat energetique cellulaire et des potentiels des differentes voies ou segments metaboliques impliques dans la production d'energie et le transport des substrats. Il n'y avait pas de difference (P > 0,05) tant pour le CERC (CON, n = 6-9; MP, n = 13) que pour le TRAP (CON, n = 6; MP, n = 13) sur le plan des concentrations (millimoles par kilogram de poids sec) d'ATP et de PCr, de lactate et de glycogene. De la meme facon, a une exception pres, les activites maximales (mole par milligram de proteine par heure) d'enzymes mitochondriales representatives du cycle de l'acide citrique (CAC), de la chaine de transport electronique, et de la [beta]-oxydation, de meme que les enzymes cytosoliques impliquees dans le transfert de phosphates riches en energie, la glycoge nolyse, la glycolyse, l'oxydation du lactate et la phosphorylation de glucose, n'etaient pas differentes (P > 0,05). Les transporteurs de glucose GLUT1 et GLUT4, et les transporteurs de monocarboxylate MCT1 et MCT4, etaient aussi normaux chez les MP. Les auteurs concluent que, en general, des anomalies sur le plan de l'etat energetique au repos et l'etat des substrats, du potentiel de differentes voies ou segments metaboliques ainsi que des transporteurs du glucose et du monocarboxylate ne semblent pas impliquees dans la pathophysiologie de la MP. [Traduit par la Redaction] Mots-cles: potentiel d'energie, transporteurs de glucose, transporteurs de monocarboxylate, muscle squelettique, microtraumatismes repetes., Introduction Work-related myalgia (WRM) is now recognized as a common clinical entity prevalent in occupations demanding highly repetitive movements at low intensity (Ranney et al. 1995; Pascarelli and Hsu 2001). [...]

We investigated the potential role of selected excitation-contraction coupling processes in females with work-related myalgia (WRM) by comparing WRM with healthy controls (CON) using tissue from extensor carpi radialis brevis (ECRB) and trapezius (TRAP) muscles. For the ECRB, age (mean [+ or -] SE) was 29.6 [+ or -] 3.5 years for CON (n = 9) and 39.2 [+ or -] 2.8 years for WRM (n = 13), while for the TRAP, the values were 26.0 [+ or -] 2.1 years for CON (n = 7) and 44.6 [+ or -] 2.9 years for WRM (n = 11). For the sarcoplasmic reticulum (SR) of the ECRB, WRM displayed concentrations (nmolfmg protein)-1-min-1) that were lower (P < 0.05) for Total (202 [+ or -] 4.4 vs 178 [+ or -] 7.1), Basal (34 [+ or -] 1.6 vs 30.1 [+ or -] 1.3), and maximal [Ca.sup.2+]-ATPase activity (Vmax, 168 [+ or -] 4.9 vs 149 [+ or -] 6.3), and [Ca.sup.2+]-uptake (5.06 [+ or -] 0.31 vs 4.13 [+ or -] 0.29), but not SERCA1a and SERCA2a isoforms, by comparison with CON. When age was incorporated as a co-variant, Total, Basal, and [Ca.sup.2+]-uptake remained different from CON (P < 0.05), but not [V.sub.max] (P = 0.13). For TRAP, none of the ATPase properties differed between groups (P > 0.05) either before or following adjustment for age. No differences (P > 0.05) were observed between the groups for [Ca.sup.2+]-release in the SR for either TRAP or ECRB. Similarly, no deficiencies, regardless of muscle, were noted for either the [Na.sup.+]-[K.sup.+]-ATPase content or the [alpha] and [beta] subunit isoform distribution in WRM. This preliminary study provides a basis for further research, with expanded numbers, investigating the hypothesis that abnormalities in SR [Ca.sup.2+] regulation are involved in the cellular etiology of WRM. Key words: myalgia, work, sarcoplasmic reticulum, calcium regulation, trapezius, extensor carpi radialis brevis, excitationcontraction coupling. Les auteurs ont examine le role potentiel de processus de couplage excitation-contraction selectionnes, chez des femmes souffrant de myalgie professionnelle (MP), en les comparant a des controles sains (CON), en utilisant des biopsies du muscle court extenseur radial du carpe (MCERC) et du trapeze (TRAP). L'age des participantes a l'etude du MCERC (moyenne [+ or -] SE) etait de 29,6 [+ or -] 3.5 ans et de 39,2 [+ or -] 2,8 ans pour les CON (n = 9) et les MP (n = 13), respectivement, alors que les participantes a l'etude du TRAP etaient agees de 26,0 [+ or -] 2,1 ans et de 44,6 [+ or -] 2,9 ans pour les CON (n = 7) et MP (n = 11). Dans le reticulum sarcoplasmique (SR) (MCERC), les sujets avec MP presentment des concentrations (nmolfmg proteine)-1-min-1) qui etaient plus faibles (P < 0,05) sur le plan de l'activite totale (202 [+ or -] 4,4 vs 178 [+ or -] 7,1), basale (34 [+ or -] 1,6 vs 30,1 [+ or -] 1,3) et maximale de la [Ca.sup.2+]- ATPase ([V.sub.max], 168 [+ or -] 4,9 vs 149 [+ or -] 6,3) et de la captation de [Ca.sup.2+] (5,06 [+ or -] 0,31 vs 4,13 [+ or -] 0,29), mais pas en ce qui concerne les isoformes SERCA1a et SERCA2a, comparativement aux controles. Lorsque l'age etait considere comme co-variable, l'activite totale et basale et la captation de [Ca.sup.2+] demeuraient differentes des CON (P < 0,05), contrairement au Vmax (P = 0,13). En ce qui concerne le TRAP, les proprietes des ATPases ne differaient pas en fonction des groupes (P > 0,05), avant ou apres l'ajustement en fonction de l'age. Aucune difference (P > 0,05) n'etait observee entre les groupes sur le plan de la liberation de [Ca.sup.2+] du SR du TRAP ou du MCERC. De la meme fa^on, aucun deficit n'etait note sur le plan du contenu en[Na.sup.+]-[K.sup.+]-ATPase ou de la distribution des isoformes des sous-unites a et p chez les sujets avec MP, quel que soit le muscle. Cette etude preliminaire jette la base d'une recherche future avec un plus grand nombre de sujets, permettant de verifier l'hypothese que des anomalies de la regulation du [Ca.sup.2+] dans le SR sont impliquees dans l'etiologie cellulaire de la MP. [Traduit par la Redaction] Mots-cles : myalgie, travail, reticulum sarcoplasmique, regulation du calcium, trapeze, muscle court extenseur radial du carpe, couplage excitation-contraction., Introduction Upper-extremity disorders affecting the muscle tissue specifically may be characterized by diffuse symptoms including localized tenderness with discomfort and pain on contraction (Ranneyet al. 1995; Visser and van Dieen [...]

To investigate fibre-type abnormalities in women with work-related myalgia (WRM), tissue samples were extracted from their trapezius (TRAP) and the extensor carpi radialis brevis (ECRB) muscles and compared with healthy controls (CON). For the ECRB samples (CON, n = 6; WRM, n = 11), no differences (P > 0.05) were found between groups for any of the properties examined, namely fibre-type (I, IIA, IIX, IIAX) distribution, cross-sectional fibre area, capillary counts (CC), capillary to fibre area ratio, and succinic dehydrogenase activity. For the TRAP samples (CON, n = 6; WRM, n = 8), the only difference (P < 0.05) observed between groups was for CC (CON > WRM), which was not statistically significant (P > 0.05) when age was used a covariant. A comparison of the properties of these 2 muscles in the CON group indicated a higher (P < 0.05) and lower (P < 0.05) percentage of type I and type IIA fibres, respectively, in the TRAP as well as higher (P < 0.05) CC, which was not specific to fibre type. These preliminary results suggest that the properties employed to characterize fibre types do not differentiate CON from WRM for either the TRAP or ECRB. As a consequence, the role of inherent fibre-type differences between these muscles in the pathogenesis of WRM remains uncertain. Key words: work-related myalgia, trapezius, extensor carpi radialis brevis, fibre types and subtypes, cross sectional area, capillarization, oxidative potential. Des echantillons de tissu musculaire ont ete preleves du trapeze (TRAP) et muscle court extenseur radial du carpe (CERC) afin d'examiner les anomalies dans les types de fibres chez des femmes souffrant de myalgie professionnelle (MP) et les comparer a des controles sains (CON). En ce qui concerne le CERC (CON, n = 6;MP, n = 11), aucune difference (P > 0,05) n'a ete trouvee entre les groupes et ce, pour aucune des proprietes examinees, notamment la distribution du type de fibres (I, IIA, IIX, IIAX), la zone de fibres en coupe transversale, le nombre de capillaires (NC), le rapport capillaires/fibres et l'activite de la succinate deshydrogenase. En ce qui concerne le TRAP (CON, n = 6;MP, n = 8), la seule difference (P > 0,05) observee entre les groupes se situait sur le plan du NC (CON > MP), qui devenait non significative (P > 0,05) lorsque l'age etait utilise comme co-variable. Une comparaison de ces proprietes entre les muscles chez les CON indiquait des pourcentages respectivement plus eleve (P > 0,05) et plus faible (P > 0,05) des fibres de type I et IIA du TRAP, de meme qu'un NC plus eleve (P > 0,05) qui n'etait pas specifique au type de fibres. Ces resultats preliminaires suggerent que les proprietes utilisees pour caracteriser le type de fibres ne permettent pas de differencier les CON des MP, ni avec le TRAP, ni le CERC. Consequemment, le role des differences inherentes sur le plan des types de fibres entre ces muscles dans la pathogenese de la MP demeure incertain. [Traduit par la Redaction] Mots-cles: myalgie professionnelle, trapeze, muscle court extenseur radial du carpe, types et sous-types de fibres, zone en coupe transversale, capillarisation, potentiel oxydant., Introduction The Cinderella hypothesis (damage to the muscles can occur when the muscle fibers that are activated first are also the last to deactivate) is a popular but controversial hypothesis [...]

We examined the influence of estrogen receptor-alpha (ERα) activation on estrogen-mediated regulation of heat shock proteins 70 (Hsp70) and 27 (Hsp27) in soleus. Ovariectomized rats received estrogen (EST), an ERα agonist (propyl pyrazole triol, PPT), both (EST+PPT), or a sham, and they served as either unexercised controls or were subjected to exercise by having to run downhill (17 m/min, -13.5° grade) for 90 min. At 72 h postexercise, soleus muscles were removed and either immunohistochemically stained for Hsp70 and myosin heavy chain or homogenized for Western blotting for Hsp70 and Hsp27. Elevated (p < 0.05) basal Hsp70 in both type I and II fibres in the unexercised EST, PPT, and EST+PPT groups relative to unexercised sham animals was noted. Compared with Hsp70 levels in the unexercised animals, that in exercised animals was elevated (p < 0.05) in both sham and PPT groups but not in EST and EST+PPT groups. Western blot determined that Hsp27 levels were not significantly different between groups. Hence, the ability of estrogen to augment resting type I and type II muscle fibre Hsp70 content is primarily mediated via muscle ERα. However, the blunted Hsp70 response following damaging exercise in estrogensupplemented animals does not appear to be fully accounted for by ERα-mediated effects. Key words: estrogen, heat shock proteins, estrogen receptors, skeletal muscle, exercise, muscle damage. Nous avons examine l'influence de l'activation du recepteur d'oestrogene-alpha (ERα) sur la regulation par l'oestrogene des proteines de choc thermique Hsp70 et Hsp27 dans le soleaire. Des rates ayant subi une ovariectomie ont recu soit de l'oestrogene (EST), un agoniste du ERα (propyl pyrazole triol, PPT), les deux (EST+PPT) ou un faux traitement, et elles ont servi de controles non entraines ou elles ont ete soumises a une course en pente (17 m/min, -13,5° d'inclinaison) pendant 90 min. Soixante-douze heures apres l'exercice, les muscles soleaires ont ete retires et colores par immunohistochimie afin de reveler la Hsp70, la chaine legere de la myosine (MHC), ou homogeneises afin de reveler la Hsp70 et la Hsp27 par buvardage Western. Un niveau de base eleve de Hsp70 (p < 0,05) a ete observe chez les animaux non entraines des groupes EST, PPT et EST+PPT, comparativement aux animaux non entraines du groupe faux traitement et ce, tant dans les fibres de type I que celles de type II. Par rapport aux animaux non entraines, l'exercice accroissait le niveau de Hsp70 (p < 0,05) chez les groupes faux traitement et PPT, contrairement aux groupes EST et EST+PPT. Aucune difference significative des niveaux de Hsp27 determines par buvardage Western n'a ete observee entre les groupes. Donc, la capacite de l'oestrogene a augmenter le contenu en Hsp70 dans les fibres musculaires de type I et II au repos fait d'abord intervenir l'ERα du muscle. Toutefois, la reponse attenuee de la Hsp70 a la suite d'un exercice dommageable chez les animaux supplementes en oestrogene ne semble pas etre totalement expliquee par des effets faisant intervenir l'ERα. [Traduit par la Redaction] Mots-cles: oestrogene, proteines de choc thermique, recepteurs d'oestrogenes, muscle squelettique, exercice, dommage musculaire., Introduction Heat shock proteins (Hsps) can be induced by various forms of stress, including oxidative damage and protein denaturation, which often accompany eccentric exercise in skeletal muscle (Welch 1992). Both [...]

Aging skeletal muscle shows an increased time to peak force and relaxation and a decreased specific force, all of which could relate to changes in muscle [Ca.sup.2+] handling. The purpose of this study was to determine if [Ca.sup.2+]-handling protein content and function are decreased in senescent gastrocnemius muscle and if initiating a training program in late middle age (LMA, 29 mo old) could improve function in senescent (34-to 36-mo-old) muscle. LMA male Fischer 344 x Brown-Norway rats underwent 5-7 mo of treadmill training. Aging resulted in a decrease in maximal sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA) activity and a decrease in [Ca.sup.2+] release rate but no change in [Ca.sup.2+] uptake rate. Efficiency of the [Ca.sup.2+] pump was increased with age, as was the content of SERCA2a. Training caused a further increase in SERCA2a content. Aging also caused an increase in protein carbonyl and reactive nitrogen species damage accumulation, and both further increased with training. Consistent with the increase in oxidative damage, heat shock protein 70 content was increased with age and further increased with training. Together, these results suggest that while initiating exercise training in LMA augments the age-related increase in expression of heat shock protein 70 and the more efficient SERCA2a isoform, it did not prevent the decrease in SERCA activity and exacerbated oxidative damage in senescent gastrocnemius muscle. aging; sarcoplasmic reticulum; nitrotyrosine; carbonylation; endurance training doi: 10.1152/ajpregu.00663.2009.

Apoptosis in skeletal muscle plays an important role in age- and disease-related tissue dysfunction. Physical activity can influence apoptotic signaling; however, this process has not been well studied in human skeletal muscle. The purpose of this study was to perform a comprehensive analysis of apoptosis-related proteins/enzymes, DNA fragmentation, and oxidative stress in skeletal muscle of humans during an acute bout of prolonged moderate-intensity exercise. Eight healthy, recreationally active individuals (age 20.8 [+ or -] 0.5 yr, [Vo.sub.2peak] 51.2 [+ or -] 0.9 ml x [kg.sup.-1] x [min.sup.-1], BMI 21.5 [+ or -] 0.8 kg/[m.sup.2]) exercised on a cycle ergometer at ~60% [Vo.sub.2peak] for 2 h. Muscle biopsies were obtained at rest as well as at 60 and 120 min of exercise. Although exercise was associated with a significant whole body and muscle metabolic response, there were no significant changes in the content of antiapoptotic (ARC, Bcl-2, Hsp70, XIAP) and proapoptotic (AIF, Bax, Smac) proteins, activity of proteolytic enzymes (caspase-3, caspase-8, caspase-9), DNA fragmentation, or TUNEL-positive nuclei in skeletal muscle. Furthermore, the protein levels of several antioxidant enzymes (catalase, CuZnSOD, MnSOD), concentrations of GSH and GSSG, and degree of ROS generation in skeletal muscle were not altered by exercise. Fiber type-specific analysis also revealed that ARC (P < 0.001) and Hsp70 (P < 0.05) protein were significantly higher in type I compared with type IIA and type IIAX/X fibers; however, protein levels were not affected by exercise. These findings suggest that a single bout of prolonged moderate-intensity aerobic exercise is not sufficient to alter apoptotic signaling in skeletal muscle of healthy humans. physical activity; cell death; oxidative stress; apoptosis repressor with caspase recruitment domain; heat shock protein 70 doi:10.1152/ajpendo.00678.2009.

In this study, we aimed to directly quantify the relative contribution of [Ca.sup.2+] cycling to resting metabolic rate in mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus.) skeletal muscle. Resting oxygen consumption of isolated muscles (V[o.sub.2], [micro]l * g [wt.sup.-1] * [s.sup.-1])) measured polarographically at 30[degrees]C was ~25% higher in soleus (0.61 [+ or -] .03) than in EDL (0.46 [+ or -] .03). To quantify the specific contribution of [Ca.sup.2+] cycling to resting metabolic rate, cyclopiazonic acid (CPA), a highly specific inhibitor of sarco(endo)plasmic reticulum [Ca.sup.2+] ATPases (SERCAs), was added to the bath at different concentrations (1, 5, 10, and 15 [micro]M). There was a concentration-dependent effect of CPA on V[o.sub.2], with increasing CPA concentrations up to 10 [micro]M resulting in progressively greater reductions in muscle V[o.sub.2]. There were no differences between 10 and 15 [micro]M CPA, indicating that 10 [micro]M CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle V[o.sub.2] in response to CPA was nearly identical in EDL (1 [micro]M, 10.6 [+ or -] 3.0%; 5 [micro]M, 33.2 [+ or -] 3.4%; 10 [micro]M, 49.2 [+ or -] 2.9%; 15 [micro]M, 50.9 [+ or -] 2.1%) and soleus (1 [micro]M, 11.2 [+ or -] 1.5%; 5 [micro]M, 37.7 [+ or -] 2.4%; 10 [micro]M, 50.0 [+ or -] 1.3%; 15 [micro]M, 49.9 [+ or -] 1.6%). The results indicate that ATP consumption by SERCAs is responsible for ~50% of resting metabolic rate in both mouse fast- and slow-twitch muscles at 30[degrees]C. Thus SERCA pumps in skeletal muscle could represent an important control point for energy balance regulation and a potential target for metabolic alterations to oppose obesity. oxygen consumption; in vitro; isolated skeletal muscle; energy expenditure; calcium pump doi:10.1152/ajpcell.00479.2009

[Ryr1.sup.I4895T/wt] (IT/+) mice express a knockin mutation corresponding to the human I4898T EC-uncoupling mutation in the type 1 ryanodine receptor/[Ca.sup.2+] release channel (RyR1), which causes a severe form of central core disease (CCD). IT/+ mice exhibit a slowly progressive congenital myopathy, with neonatal respiratory stress, skeletal muscle weakness, impaired mobility, dorsal kyphosis, and hind limb paralysis. Lesions observed in myofibers from diseased mice undergo age-dependent transformation from minicores to cores and nemaline rods. Early ultrastructural abnormalities include sarcomeric misalignment, Z-line streaming, focal loss of cross-striations, and myofibrillar splitting and intermingling that may arise from defective myofibrillogenesis. However, manifestation of the disease phenotype is highly variable on a Sv129 genomic background. Quantitative RT-PCR shows an equimolar ratio of WT and mutant Ryr1 transcripts within IT/+ myofibers and total RyR1 protein expression levels are normal. We propose a unifying theory in which the cause of core formation lies in functional heterogeneity among RyR1 tetramers. Random combinations of normal and either leaky or EC-uncoupled RyR subunits would lead to spatial differences in [Ca.sup.2+] transients; the resulting heterogeneity of contraction among myofibrils would lead to focal, irreversible tearing and shearing, which would, over time, enlarge to form minicores, cores, and nemaline rods. The IT/+ mouse line is proposed to be a valid model of RyR1-related congenital myopathy, offering high potential for elucidation of the pathogenesis of skeletal muscle disorders arising from impaired EC coupling. calcium | central core disease | multiminicore disease | nemaline rod myopathy | ryanodine receptor doi/10.1073/pnas.0912126106

Pancreatic β-cells can secrete insulin via 2 pathways characterized as KATP channel -dependent and -independent. The KATP channel–independent pathway is characterized by a rise in several potential metabolic signaling molecules, including the NADPH/NADP+ ratio and α-ketoglutarate (αKG). Prolyl hydroxylases (PHDs), which belong to the αKG-dependent dioxygenase superfamily, are known to regulate the stability of hypoxia-inducible factor α. In the current study, we assess the role of PHDs in vivo using the pharmacological inhibitor dimethyloxalylglycine (DMOG) and generated β-cell-specific knockout (KO) mice for all 3 isoforms of PHD (β-PHD1 KO, β-PHD2 KO, and β-PHD3 KO mice). DMOG inhibited in vivo insulin secretion in response to glucose challenge and inhibited the first phase of insulin secretion but enhanced the second phase of insulin secretion in isolated islets. None of the β-PHD KO mice showed any significant in vivo defects associated with glucose tolerance and insulin resistance except for β-PHD2 KO mice which had significantly increased plasma insulin during a glucose challenge. Islets from both β-PHD1 KO and β-PHD3 KO had elevated β-cell apoptosis and reduced β-cell mass. Isolated islets from β-PHD1 KO and β-PHD3 KO had impaired glucose-stimulated insulin secretion and glucose-stimulated increases in the ATP/ADP and NADPH/NADP+ ratio. All 3 PHD isoforms are expressed in β-cells, with PHD3 showing the most distinct expression pattern. The lack of each PHD protein did not significantly impair in vivo glucose homeostasis. However, β-PHD1 KO and β-PHD3 KO mice had defective β-cell mass and islet insulin secretion, suggesting that these mice may be predisposed to developing diabetes. [ABSTRACT FROM AUTHOR]

Author(s): Daniel Gamu [1]; A Russell Tupling (corresponding author) [1] Adaptive thermogenesis refers to the activation of mechanisms that generate heat for the purpose of regulating body temperature or metabolism [...]