Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with α-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 ± 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey.

Antibody microprobes were used to study release of immunoreactive neurokinins in the dorsal horn of the anaesthetized spinal cat following sustained isometric contraction of ipsilateral hindlimb muscles. Microprobes had immobilized antibodies to neurokinin A (NKA) on their outer surfaces and bound a proportion of released molecules when inserted in the central nervous system. Bound molecules were detected in autoradiographs as zones of reduced binding of 125I-NKA in which microprobes were incubated after withdrawal from the spinal cord. The left hindlimb was immobilized using an epoxy bandage splint and isometric contraction of muscles induced by intermittent tetanic stimulation of a ventral root. A basal presence of immunoreactive neurokinins was detected and this was increased by sustained isometric muscle contraction. It is probable that ergoreceptors contain and release neurokinins.

Smooth muscle contraction regulates the size of the blood vessel lumen which directly affects the mechanical response of the vessel. Folding in arteries has been observed in arteries during excessive contraction, known as a coronary artery spasm. The interplay of muscle contraction, geometry, and material responses and their effects on stability can be understood through mathematical models. Here, we consider a three-layer cross-sectional model of a coronary artery with anisotropic properties and intimal thickening, and perform a linear stability analysis to investigate the circumferential folding patterns that emerge due to muscle contraction. Our model shows that a critical level of contractile activity yields a uniform strain distribution across the arterial wall. When the muscle is contracted above this critical level, the tissue behaves isotropically and it is more prone to circumferential instability. This theoretical framework could serve as a valuable tool to understand the relationship between arterial lumen morphology and wall contraction in health and disease.

No description available.

<p> A novel method has been developed to determine the quantitative relationship between the percentage ofla fibres stimulated synchronously, and the percentage of human flexor carpi radialis (FCR) motoneurons (MNs) discharged reflexly. The method assumes a normal distribution of Ia fibre thresholds to electrical stimulation. Among the 11 healthy subjects tested during relaxation, there were considerable differences in the reflex excitability of the FCR MNs to quantitative Ia fibre inputs. The Ia fibre input-FCR MN output curves were either initially steeply-rising, initially slowly-rising, or initially and latterly steeply-rising. When the results were averaged, however, the curve for the 11 subjects in the relaxed state appeared to be fairly linear throughout the entire range of the Ia fibre inputs, and a mean of82% of the Ia fibres discharged approximately 20% of theMNs. </p> <p> Regardless of the variability in the shape of individual input-output curves during relaxation, potentiation of the FCR MN output was observed during weak wrist flexion in 10 of the 11 subjects over the full range of the Ia fibre inputs. In contrast, a depression of the MN output was exhibited in all 8 subjects who weakly contracted the extensors over the full range of the Ia fibre inputs. The changes in the Ia input-MN output relationship in going from rest to voluntary contractions of wrist muscles are thought to reflect modulation by presynpatic inhibition of the Ia terminals. With very large Ia inputs during wrist extension, however, there is a steep rise in the input-output curve, which could indicate a decrease in presynaptic inhibition of Ia terminals in the FCR muscle. The modulation ofthe input-output relationship observed in the present study is consistent with the task-dependent differences of reflex excitability observed by Stein et al. (1988). </p> / Thesis / Master of Applied Science (MASc)

The SH3 and cysteine rich domain 3 (Stac3) gene is expressed specifically in skeletal muscle and essential for skeletal muscle contraction and postnatal life in mice. In this dissertation project, I conducted two studies to further understand the role of STAC3 in skeletal muscle development, growth, and contraction. In the first study, I compared the contractile responses of hindlimb muscles of Stac3 knockout and control mice to electrical stimulation, high [K+]-induced membrane depolarization, and caffeine and 4-chloro-m-cresol (4-CMC) activation of ryanodine receptor (RyR). Frequent electrostimulation-, high [K+]-, 4-CMC- and caffeine-induced maximal tensions in Stac3-deleted muscles were approximately 20%, 29%, 58% and 55% of those in control muscles, respectively. 4-CMC- and caffeine-induced increases in intracellular calcium were not different between Stac3-deleted and control myotubes. Myosin-ATPase and NADH-tetrazolium reductase staining as well as gene expression analyses revealed that Stac3-deleted hindlimb muscles contained more slow type-like fibers than control muscles. These data together confirm a role of STAC3 in EC coupling but also suggest that defective EC coupling is only partially responsible for the significantly reduced contractility in Stac3-deleted hindlimb muscles. In the second study, I determined the potential role of STAC3 in postnatal skeletal muscle growth, fiber composition, and contraction by disrupting Stac3 gene expression in postnatal mice through the Flp-FRT and tamoxifen-inducible Cre-loxP systems. Postnatal Stac3 deletion inhibited body and limb muscle mass gains. Histological staining and gene expression analyses revealed that postnatal Stac3 deletion decreased the size of myofibers and increased the percentage of myofibers containing centralized nuclei without affecting the total myofiber number. Postnatal Stac3 deletion decreased limb muscle strength. Postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced maximal force output in limb muscles. Similarly, postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced calcium release from the sarcoplasmic reticulum. These results demonstrate that STAC3 is important to myofiber hypertrophy, myofiber type composition, contraction, and EC coupling in postnatal skeletal muscle. / Ph. D.

The purpose of this research was to study the relationship between muscle coordination and the performance of a simple manual tracking task. The study employed an isometric, zero order, pursuit tracking task with a laterally translating, periodic sine wave forcing function. The speed of the target was varied by altering the Frequency (3 levels) of the simple sine wave. The control/response ratio for each trial was manipulated by requiring a percentage of each subject’s flexion and extension maximum voluntary contraction effort (MVC, 5 levels) to track the target. Multiple electromyograms (EMGs) of the biceps and triceps muscle groups were taken to observe flexor and extensor activity during the tracking task. Muscle modeling techniques were used to quantify the force contributions from the biceps and triceps to the observed tracking force. It was hypothesized that significant levels of co-active muscle effort would be present during the tracking task and that this co-contraction would have a unique characteristic function about the tracking conditions which yielded optimal tracking performance. The dependent measures investigated were the absolute tracking error as a proportion of the required tracking force (proportional error, PE), the absolute antagonist muscle force (AAF), and the ratio of antagonist to agonist force (co-contraction ratio, CR). Each muscle group’s maximum muscle force (MMF) required to track each condition was also determined. The experimental design was a 3 by 5 by 2 mixed factor, repeated measures ANOVA with Gender (5 male, 5 female) as the blocking variable. The ANOVA results revealed that both target Frequency and tracking Force level had significant effects on tracking error (PE). Orthogonal polynomial contrasts showed that the Frequency effect was characteristically linear while the Force effect was quadratic in nature. A polynomial regression function was used to predict PE from the Force and Frequency conditions. This model accounted for over 96% of the variance in the PE cell means. Further analysis revealed the optimal Force level for isometric tracking to be approximately 61% MVC. Analysis of the force contributions from each muscle group revealed quadratic relationships for the actual muscle force (%MMF) of the biceps during flexion and of the triceps during extension. These results show that optimal tracking performance during flexion occurs at approximately 66% of the biceps MMF and 65% of the triceps MMF during extension. Actual MMF values were consistently larger than net force values indicating that due to the presence of co-contraction, the measured force output at the wrist underestimated the actual muscle forces involved in tracking. Neither Force nor Frequency had significant effects on absolute co-activity (AAF) showing that antagonist activity remained largely constant over the tracking conditions. However, co-activity was higher for the extension phase than for the flexion phase of the task. Both Force and Frequency had significant effects on the co-contraction ratio (CR). However, no characteristic function of co-activity was found to explain the optimal tracking performance at median levels of flexion and extension force. CR increased with increasing target speed (Frequency) while it decreased with higher tracking Force levels. Since antagonist activity (AAF) remained almost constant, these results for CR must be due to changes in the level of agonist activity needed to perform the tracking task. Higher co-contraction was also found during decreasing force production (release) than for increasing force production (exertion). Since there was no significant difference in tracking error for these parts of the task, co-activity may serve to facilitate tracking performance by controlling the rate of force release. / Master of Science

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Le but de cette dissertation doctorale était de mieux comprendre les mécanismes de contrôle tant centraux que périphériques qui sont à l’origine de la régulation neuromusculaire lors de mouvement impliquant des contractions de type excentrique. Lors d’une première étude réalisée sur le muscle jambier antérieur, nous avons montré qu’un exercice utilisant des contractions excentriques présentait une meilleure résistance à la fatigue que lorsque des contractions concentriques étaient impliquées puisque celui-ci conduit à une moindre diminution du couple de force et de l’activité électromyographique. L’absence de fatigue nerveuse centrale et l’observation d’un comportement spécifique du couple de force et de l’activité électromyographique lors de ces épreuves de fatigue semblait traduire la mise en jeu de processus périphériques différents. La plus grande fatigue observée lors de l’épreuve concentrique suggérait une activation plus importante que pour l’épreuve excentrique, dont les conséquences métaboliques renforcent les altérations du couplage excitation-contraction. Dans un second temps, nous avons étudié l’effet des modifications de longueur de fascicule du muscle jambier antérieur sur le comportement spécifique des unités motrices (ordre, fréquence et seuil de recrutement) lors de contractions isométriques. Nous avons ensuite analysé le comportement d’unités motrices selon les différentes modalités de contractions (concentrique vs. excentrique) sur ce même muscle. Pour y répondre, différentes techniques d’analyse ont été utilisées dont l’enregistrement électromyographique intramusculaire et l’ultrasonographie. Enfin, nous avons cherché à analyser l’évolution des différents mécanismes de régulation d’origine périphérique et /ou central susceptible de modifier l’excitabilité du pool de motoneurone lors de contractions concentriques et excentriques. Pour y répondre, les modulations d’une part, du réflexe de Hoffmann (réflexe H) par stimulation électrique et d’autre part, celles du potentiel moteur évoqué (MEP) par stimulation magnétique transcorticale, ont été investiguées. Ces réponses ont été enregistrées à différents angles de la plage articulaires étudiée lors des contractions concentriques et excentriques, ainsi qu’aux deux extrémités angulaires lors de contraction isométriques. Notre travail indique que l’ordre de recrutement des unités motrices entre les contractions concentriques et excentriques étant identique, le système nerveux n’utilise qu’une seule et même stratégie d’activation liée à la taille des motoneurones impliqués dans ces deux types de contractions. En outre, les contractions excentriques lorsqu’elles sont réalisées à vitesse constante, sont associées à une modulation spécifique de la fréquence de décharge des unités motrices. Ce comportement diffère de celui observé lors de contractions concentriques, malgré une modification linéaire et similaire de la longueur des fascicules et du couple de force au cours de ces deux tâches. Les modulations du recrutement des unités motrices semblent davantage dépendre de la longueur musculaire tandis que les modulations de fréquence prédominent pendant les contractions en raccourcissement. Ce comportement spécifique semble dépendant de mécanismes de régulation principalement localisés au niveau spinal. Ainsi, le degré d’inhibition des afférences fusoriales affectant le pool de motoneurones du muscle tibial antérieur lors de sollicitations actives du muscle, dépend davantage de l’angle articulaire et donc de la longueur du muscle plutôt que du mode de contraction. Lors de sollicitations isométriques, le retour sensoriel Ia est principalement contrôlé au niveau présynaptique en fonction de la longueur du muscle. Lors de sollicitations concentriques et excentriques, ces mécanismes présynaptiques réguleraient l'excitabilité spinale de manière similaire entre les deux modes. Néanmoins, bien que l'inhibition présynaptique soit probablement plus marquée lors des sollicitations excentriques, ce mode de contraction semble également régulé par des mécanismes d'inhibition intervenant au niveau postsynaptique tel que l'inhibition récurrente de Renshaw. Ce mécanisme localisé au niveau postsynaptique permettrait de réguler la fréquence de pulsation des unités motrices lors de sollicitations excentriques dans le but le faciliter l'exécution du mouvement. L'originalité de notre travail a été d’étudier le comportement d’une même unité dans les deux modes de contractions alors que la méthode d’analyse généralement adoptée consistait à comparer des populations d’unités motrices entre-elles. De plus, les changements de la longueur du muscle au cours du mouvement ainsi que les vitesses de raccourcissement ou d'allongement ont été estimés à partir de la mesure directe de la longueur des fascicules musculaires. Cette dernière présente l’avantage de fournir une information de longueur et de vitesse sur la portion de muscle à partir de laquelle les enregistrements d’unités motrices ont été obtenus. Enfin, étant donné les modulations possibles tant au niveau spinal que supraspinal des mécanismes nerveux mis en jeu, il semblait important d’analyser celles-ci pendant le mouvement et aux différents angles investigués. Cette précision méthodologique a permis d'élargir la discussion concernant les possibles modifications de la balance "excitation-inhibition" lors de sollicitations excentriques, qui, jusqu’à présent, n'avaient été analysées que pour un angle articulaire donné. / Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished

Titin is a giant protein spanning from the Z-disk to the M-band of the cardiac sarcomere. In the I-band titin acts as a molecular spring, contributing to passive mechanical characteristics of the myocardium throughout a heartbeat. RNA Binding Motif Protein 20 (RBM20) is required for normal titin splicing, and its absence or altered function leads to greater expression of a very large, more compliant N2BA titin isoform in Rbm20 homozygous mice (Rbm20(Delta RRm)) compared to wild-type mice (WT) that almost exclusively express the stiffer N2B titin isoform. Prior studies using Rbm20(Delta RRm) animals have shown that increased titin compliance compromises muscle ultrastructure and attenuates the Frank-Starling relationship. Although previous computational simulations of muscle contraction suggested that increasing compliance of the sarcomere slows the rate of tension development and prolongs cross-bridge attachment, none of the reported effects of Rbm20(Delta RRm) on myocardial function have been attributed to changes in cross-bridge cycling kinetics. To test the relationship between increased sarcomere compliance and cross-bridge kinetics, we used stochastic length-perturbation analysis in Ca2+-activated, skinned papillary muscle strips from Rbrn20<^>R'Rm and WT mice. We found increasing titin compliance depressed maximal tension, decreased Ca2+-sensitivity of the tension-pCa relationship, and slowed myosin detachment rate in myocardium from Rbm20(Delta RRm) vs. WT mice. As sarcomere length increased from 1.9 to 2.2 mu m, length-dependent activation of contraction was eliminated in the Rbrn20<^>R'Rm myocardium, even though myosin MgADP release rate decreased similar to 20% to prolong strong cross-bridge binding at longer sarcomere length. These data suggest that increasing N2BA expression may alter cardiac performance in a length-dependent manner, showing greater deficits in tension production and slower cross-bridge kinetics at longer sarcomere length. This study also supports the idea that passive mechanical characteristics of the myocardium influence ensemble cross-bridge behavior and maintenance of tension generation throughout the sarcomere.