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Influences of repetitive muscle contractions with different modes on tendon elasticity in vivo.

The present study aimed to investigate the effects of repetitive muscle contractions on the elasticity of human tendon structures in vivo. Before and after each endurance test, the elongation of the tendon and aponeurosis of vastus lateralis muscle (L) was directly measured by ultrasonography while the subjects performed ramp isometric knee extension up to maximal voluntary isometric contraction (MVC). Six male subjects performed muscle endurance tests that consisted of knee extension tasks with four different contraction modes: 1) 50 repetitions of maximal voluntary eccentric action for 3 s with 3 s of relaxation (ET1), 2) three sets of 50 repetitions of MVC for 1 s with 3 s of relaxation (ET2), 3) 50 repetitions of MVC for 3 s with 3 s of relaxation (ET3), and 4) 50 repetitions of 50% MVC for 6 s with 6 s of relaxation (ET4). In ET1 and ET2, there were no significant differences in L values at any force production levels between before and after endurance tests. In the cases of ET3 and ET4, however, the extent of elongation after the completion of the tests tended to be greater. The L values above 330 N in ET3 and 440 N in ET4, respectively, were significantly greater after endurance tests than before. These results suggested that the repeated longer duration contractions would make the tendon structures more compliant and that the changes in the elasticity might be not be affected by either muscle action mode or force production level but by the duration of action.

Adult↗

Calcium dependence of myosin phosphorylation and airway smooth muscle contraction and relaxation.

The time course and the steady-state calcium dependence of myosin phosphorylation and isotonic shortening velocity were studied during contraction and relaxation of canine tracheal smooth muscle. Dephosphorylation of myosin coincided with the decay of isotonic shortening velocity during rapid relaxation following agonist washout. However, the decay of shortening velocity preceded dephosphorylation during a slow relaxation induced by Ca2+-free physiological salt solution (PSS). Carbachol dose-response curves for isometric stress development and myosin phosphorylation were superimposable but shifted to the left of the shortening velocity dose-response. The steady-state Ca2+ dependence of myosin phosphorylation was defined using carbachol and K+ as agonists. There was a significant dissociation of dephosphorylation and relaxation following a stepwise reduction of extracellular CaCl2 concentration. This result was related to muscarinic activation because the dissociation of relaxation and dephosphorylation was reduced by atropine in muscles stimulated with K+. Myosin phosphorylation was completely dissociated from contraction when muscles were stimulated with carbachol in Ca2+-free PSS and contracted by readmission of CaCl2. Mechanisms in addition to myosin phosphorylation appear to regulate airway muscle tone and shortening velocity, and two possibilities are discussed.

Acetylcholine↗

Altered muscle activation patterns in symptomatic women during pelvic floor muscle contraction and Valsalva manouevre.

AIMS: To investigate the muscle activation patterns of the abdomino-pelvic region used by incontinent women during a pelvic floor muscle (PFM) contraction and a Valsalva manouevre compared to healthy, asymptomatic subjects. METHODS: Thirteen incontinent (symptomatic) women, identified using ultrasound to be consistently depressing the bladder base during PFM contraction, and thirteen continent women (asymptomatic) able to perform an elevating PFM contraction were assessed using surface electromyography (EMG) of the PFM, abdominal and chest wall muscles and vaginal and intra-abdominal pressure (IAP) measurements during PFM contraction and Valsalva under ultrasound surveillance. RESULTS: There were no differences between groups in age, parity or BMI. There was a difference in muscle activation patterns between groups (P = 0.001). During PFM contraction the PFM were less active and the abdominal and chest wall muscles were more active in the symptomatic group. During Valsalva, the PFM and EO were more active in the symptomatic group but there was no difference in the activation of the other muscles between groups. There was a significant interaction (group x pressure) for change in IAP (P = 0.047) but no significant interaction for change in vaginal pressure (VP) (P = 0.324). CONCLUSIONS: The symptomatic women displayed altered muscle activation patterns when compared to the asymptomatic group. The symptomatic women were unable to perform a voluntary PFM contraction using a localized muscle strategy, instead activating all the muscles of the abdomino-pelvic cavity. The potential for muscle substitution strategies reinforces the need for close attention to specificity when prescribing PFM exercise programs.

Adult↗

Simple modelling of linear and nonlinear mechanical responses to sinusoidal oscillations during muscle contraction.

The mechanical responses of muscle to sinusoidal oscillations were analysed using a contraction model based on Huxley's 1957 model. To reproduce the three well-documented exponential processes resolved in the course of sinusoidal analysis, a few modifications had to be made on the original Huxley's model: (1) Each myosin cross-bridge should support substantial force at its position where the rate of detachment (g) abruptly changes. (2) Each cross-bridge should have the capability of stress-relaxation while attached to actin. This stress-relaxation should occur with a rate constant greater than the overall turnover rate of cross-bridges. After these modifications, the model reproduces not only the three exponential processes, but also the nonlinearity in the mechanical response, which is derived from the asymmetrical dependence of the rate constants on the cross-bridge strain. The present study provides a simplest model which reproduces the linear and nonlinear responses to sinusoidal oscillations, and help relate the exponential processes to the underlying attachment/detachment steps in the cross-bridge cycle.

Animals↗

Oscillatory cortical drive to isometrically contracting muscle in Unverricht-Lundborg type progressive myoclonus epilepsy (ULD).

OBJECTIVE: We investigated with whole-scalp magnetoencephalography (MEG) oscillatory cortical drive to isometrically contracting muscle in 8 genetically verified, and thus etiologically homogeneous, Unverricht-Lundborg type progressive myoclonus epilepsy (ULD) patients suffering from cortical myoclonus and generalized tonic-clonic seizures. The results were compared with those of 8 healthy control subjects. METHODS: Cortical MEG signals were measured simultaneously with surface electromyography (EMG) during isometric contraction of the left and right first dorsal interosseus muscles. Cortex-muscle coherence and cross-correlograms between MEG and EMG signals were calculated as indicators of oscillatory cortical drive to muscle. The cortical areas involved in the maximum cortex-muscle coherence were also identified. RESULTS: In patients, the strengths of the dominant coherent peaks were 2-4 fold compared with the healthy controls. Whereas the coherence was found strictly in the contralateral primary motor cortex in controls, additional coherent activity was observed ipsilaterally in 5 out of 8 patients. CONCLUSIONS: The remarkably increased MEG-EMG coherence in ULD patients suggests altered oscillatory cortical drive to the muscle during isometric contraction. We suggest that the enhanced cortex-muscle coherence in ULD patients reflects reduced inhibition in the motor cortex, and may contribute to disturbed voluntary movements.

Adolescent↗

Nicotine-induced airway smooth muscle contraction: neural mechanisms involving the airway epithelium. Functional and histologic studies in vitro.

To assess the mechanism of and the role of the epithelium in nicotine-induced bronchoconstriction in vitro, we performed a combined functional and histologic study. Functional study: We suspended tracheal strips or rings from 16 ferrets (1124 +/- 561 g, mean +/- SD) in organ baths. Alternate tracheal strips had their epithelium removed. Dose-response curves to acetylcholine (ACh) and nicotine were established for pairs of tissues with and without epithelium, each pair receiving only one dose of nicotine. Nicotine induced brief muscle contractions not exceeding 25% of the ACh-induced maximum. Contractions were blocked by hexamethonium and 10(-7) M atropine and were abolished or inhibited strongly by tetrodotoxin (TTX), suggesting the involvement of nicotinic neuronal and muscarinic smooth muscle receptors. Removal of the epithelium strongly inhibited contractions at concentrations of nicotine greater than 3 x 10(-5) M which completely removed any dose-response effect. ACh-induced contractions were unchanged, demonstrating smooth muscle integrity. We suggest that the removal of the epithelium attenuates nicotine-induced bronchoconstriction through the removal of nerves running in or close to the epithelium. Histologic study: In tracheae from 15 ferrets (8 male, 7 female), mean weight (+/- SD) 1288 (+/- 470) g, we examined 4 techniques of epithelium removal: (1) gentle scraping with a scalpel blade moved backwards (away from the cutting edge), (2) moving a Q-tip through the unopened tracheal tube without lateral pressure, and (3, 4) stroking the mucosa of opened tracheal segments with a Q-tip, exerting (3) light or (4) moderate pressure. All methods were equally (97%-100%) efficient in removing the epithelium but differed in the amount of damage caused to the basement membrane and/or submucosal tissue. Method (2) caused less damage to the basement membrane than the other methods but still removed almost one-third of it. The study showed that complete removal of the epithelium is at the expense of the submucosa and that a given result of "epithelium removal" is also attributable to removal of the neighboring subepithelial structures.

Acetylcholine↗

Changes in electromyogram during upper limb muscle contraction induced by resistive loaded breathing in humans.

Expiratory only resistive loaded breathing (RL) reduces high energy electromyogram (EMG) power (EH) during an isometric contraction of a leg extensor muscle, but not an arm flexor. An interaction between afferent activity during expiratory RL and inspiratory non-loaded phases of breathing, which the contraction spanned, could have accounted for the reduced EH in these long contractions. Therefore this study tested the hypothesis that brief arm extensor muscle contractions (70% of maximal force), performed during a single phase of expiratory RL, would also exhibit reduced EH. Surprisingly, EH in triceps, but not biceps brachii was reduced significantly when the contraction was performed during inspiratory RL rather than expiratory RL. The results suggest that either (a) short and prolonged contractions or (b) motor drive to arm and leg extensors are affected differently by RL.

Adult↗

Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats.

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.

Animals↗

The relation between muscle contraction and metabolism: studies by 31P nuclear magnetic resonance spectroscopy.

We have used 31P nuclear magnetic resonance spectroscopy (31PNMRS) to study the relation between metabolism and contraction in frog skeletal muscle. Our results show a close association between [H2PO4(1-)] and both contractile and metabolic characteristics of muscle. We suggest that this metabolite links energy requiring to energy yielding function by participating in intermediate reactions which help to determine the rates of both processes. The observed relation between [H2PO4(1-)] and force production is consistent with the suggestion of Hibberd and colleagues, that Pi is reversibly released during the transition to the major force-producing actomyosin ATPase state. Our results also suggest that force fatigue is due to the buildup of the [H2PO4(1-)] product of ATP hydrolysis and that the effect of pH on force production is largely the result of altering H2PO4(1-)/HPO4(2-). We have found that it is the extent of glycogenolysis rather than the maximum activities of glycogenolytic enzymes that determines how much glycogen is broken down following anaerobic contraction. The most likely explanation for our results is that the ATP-forming reactions of glycolysis come to equilibrium during metabolic recovery from contraction under anaerobic conditions.

Animals↗

X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction.

To clarify the extensibility of thin actin and thick myosin filaments in muscle, we examined the spacings of actin and myosin filament-based reflections in x-ray diffraction patterns at high resolution during isometric contraction of frog skeletal muscles and steady lengthening of the active muscles using synchrotron radiation as an intense x-ray source and a storage phosphor plate as a high sensitivity, high resolution area detector. Spacing of the actin meridional reflection at approximately 1/2.7 nm-1, which corresponds to the axial rise per actin subunit in the thin filament, increased about 0.25% during isometric contraction of muscles at full overlap length of thick and thin filaments. The changes in muscles stretched to approximately half overlap of the filaments, when they were scaled linearly up to the full isometric tension, gave an increase of approximately 0.3%. Conversely, the spacing decreased by approximately 0.1% upon activation of muscles at nonoverlap length. Slow stretching of a contracting muscle increased tension and increased this spacing over the isometric contraction value. Scaled up to a 100% tension increase, this corresponds to a approximately 0.26% additional change, consistent with that of the initial isometric contraction. Taken together, the extensibility of the actin filament amounts to 3-4 nm of elongation when a muscle switches from relaxation to maximum isometric contraction. Axial spacings of the layer-line reflections at approximately 1/5.1 nm-1 and approximately 1/5.9 nm-1 corresponding to the pitches of the right- and left-handed genetic helices of the actin filament, showed similar changes to that of the meridional reflection during isometric contraction of muscles at full overlap. The spacing changes of these reflections, which also depend on the mechanical load on the muscle, indicate that elongation is accompanied by slight changes of the actin helical structure possibly because of the axial force exerted by the actomyosin cross-bridges. Additional small spacing changes of the myosin meridional reflections during length changes applied to contracting muscles represented an increase of approximately 0.26% (scaled up to a 100% tension increase) in the myosin periodicity, suggesting that such spacing changes correspond to a tension-related extension of the myosin filaments. Elongation of the myosin filament backbone amounts to approximately 2.1 nm per half sarcomere. The results indicate that a large part (approximately 70%) of the sarcomere compliance of an active muscle is caused by the extensibility of the actin and myosin filaments; 42% of the compliance resides in the actin filaments, and 27% of it is in the myosin filaments.

Actins↗

Effect of hyperglycaemia on muscle glycogen mobilization during muscle contractions in the rat.

In the rat, muscle glycogen is mobilized during the first stage of exercise, despite normoglycaemia. The aim of the present study was to examine if this process could be prevented or reduced by hyperglycaemia. Three experiments were carried out: in the first, rats were forced to run on a treadmill; in the second the gastrocnemius muscle group was made to contract by stimulation of the sciatic nerve and in the third adrenaline was administered subcutaneously. Each group was divided into two subgroups: control and enriched with glucose (hyperglycaemic). It was shown that hyperglycaemia has no effect on running-induced glycogen mobilization in hind-limb muscles of different fibre composition but prevented it totally in diaphragm muscle. Hyperglycaemia also did not affect the glycogen mobilization induced by stimulation of the sciatic nerve. However, it delayed and reduced markedly the glycogenolytic effect of adrenaline. It is concluded that increased glycogenolysis in muscles at the beginning of exercise may be a consequence of a delay in the activation of glucose transporting mechanisms in muscle cells.

Animals↗

Fast skeletal muscle troponin T increases the cooperativity of transgenic mouse cardiac muscle contraction.

1. To investigate the functional significance of different troponin T (TnT) isoforms in the Ca2+ activation of muscle contraction, transgenic mice have been constructed with a chicken fast skeletal muscle TnT transgene driven by a cardiac alpha-myosin heavy chain gene promoter. 2. Cardiac muscle-specific expression of the fast skeletal muscle TnT has been obtained with significant myofibril incorporation. Expression of the endogenous cardiac muscle thin filament regulatory proteins, such as troponin I and tropomyosin, was not altered in the transgenic mouse heart, providing an authentic system for the functional characterization of TnT isoforms. 3. Cardiac muscle contractility was analysed for the force vs. Ca2+ relationship in skinned ventricular trabeculae of transgenic mice in comparison with wild-type litter-mates. The results showed unchanged pCa50 values (5.1 +/- 0.04 and 5.1 +/- 0.1, respectively) but significantly steeper slopes (the Hill coefficient was 2.0 +/- 0.2 vs. 1.0 +/- 0.2, P < 0.05). 4. The results demonstrate that the structural and functional variation of different TnT isoforms may contribute to the difference in responsiveness and overall cooperativity of the thin filament-based Ca2+ regulation between cardiac and skeletal muscles.

Algorithms↗

Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon.

We have investigated the effects of adrenomedullin (AM) on mucosal ion transport using the Ussing method and smooth muscle contraction using the Magnus method in rat. Our results indicate that AM increases Isc (short-circuit current) for Cl- secretion (100 nM:170.0 +/- 41.2%, 1 microM:193.8 +/- 45.5%, 100% Isc:28.2 +/- 3.1 microA/cm2) with an initial small decrease of Isc, inhibiting Na+ absorption. Tetrodotoxin (TTX) inhibits the Isc response elicited by AM (86%). In addition, AM relaxes potassium-induced contraction (10 nM:11.1 +/- 8.51%, 100 nM:33.4 +/- 12.7%, 100% contraction: 1.8 +/- 0.22 g), and TTX inhibits the response elicited by AM (90%). We conclude that AM modulates water and ion transport as well as bowel movement, mainly through the colonic nervous system.

Adrenomedullin↗

A revisitation on the mechanism of action of KCl-induced vascular smooth muscle contraction: a key role of cation binding to the plasma membrane.

Aortic rings of Sprague-Dawley rats developed reproducible contractions in Ca-free, nominally Mg-free (2 microM), Na-free, K solution, but not in Ca-free, nominally Mg-free, K-free, Na solution. Further reduction of the residual Mg by 0.5 mM EDTA in the above solutions potentiated this K-induced contraction and allowed the development of a relatively small contraction in Na-rich medium, respectively. The amplitude of EDTA-enhanced, K-induced contraction was almost the same as the amplitude of contraction induced in K-rich ([K] = 142 mM), Ca-containing (2.5 mM) solution. Such K-induced contraction was completely inhibited by 38 mM Na and by 3 mM of Mg (and Ni or Cd). Nifedipine (1 microM) also inhibited aortic smooth muscle contraction produced in K-EDTA, Ca-free solution. Modulators of Ca in sarcoplasmic reticulum (ryanodine, caffeine and norephinephrine), Ca-ionophore (A-23187) and protein kinase C inhibitor (Calphostin C) had no effect on EDTA-enhanced, K-induced contraction. It was suggested that K-induced contraction in rat aorta is not dependent on the increase in cytosolic Ca following membrane depolarization, is not a result of the release of Ca from intracellular stores, and is not due to change of Ca sensitivity upon the activation of protein kinase C. We propose that the competition of K for Mg and Na at external binding sites on the plasma membranes of the smooth muscle cells is primarily responsible for the development of vascular contraction.

Animals↗

Ionic mechanisms underlying spontaneous muscle contractions in the liver fluke, Fasciola hepatica.

Spontaneous contractions of liver fluke muscle were abolished in Ca(2+)-free saline and by 100 microM nifedipine and reduced by 5 mM cadmium chloride, suggesting that they are dependent on extracellular Ca(2+). Caffeine (5 mM) significantly increased contraction amplitude and frequency. Ryanodine (100 microM) failed to block the caffeine response but significantly reduced spontaneous contraction frequency, suggesting that intracellular stores have a functional role. Cyclopiazonic acid (5 microM) had no effect on the caffeine response or spontaneous activity. 3-Isobutyl-1-methylxanthine (IBMX), forskolin, and 8-bromoadenosine 3',5'-cyclic monophosphate significantly increased spontaneous contractions, which implies that cAMP has a regulatory function in motility. Caffeine, however, produced no measurable increase in cAMP. The caffeine effect was inhibited by cadmium chloride and nifedipine, whereas IBMX-induced increases in amplitude were reduced by cadmium chloride. Thus caffeine and cAMP appear capable of opening plasma membrane Ca(2+) channels, but the involvement of cAMP in caffeine responses has not been proved.

Animals↗

Dynamic cooperativity of molecular processes in active streaming, muscle contraction, and subcellular dynamics: the molecular mechanism of self-organization at the subcellular level.

Life phenomena are a kind of ordered dynamics appearing in macroscopic systems, living systems. Schrödinger has proposed a molecular mechanism for the organization of life phenomena, i.e., 'order-from-order' mechanism where ordered dynamics are composed of molecular dynamics having order as the ordered dynamics of a watch is caused by orderly movements of its mechanical elements. However, neither evidence supporting the 'order-from-order' mechanism has been found in living systems nor the reason why molecular dynamics acquire order instead of disorder has been elucidated for more than 30 years. The latter is quite anomalous from the point of views of thermodynamics, which is based on disordered behaviors of molecules. In this paper, we verify from studies of a streaming system reconstituted from rabbit skeletal F-actin and HMM that one life phenomenon, active streaming, is caused by the 'order-from-order' mechanism. This is also the case for muscle contraction. Moreover, it is probable that this mechanism generally works at the subcellular level, not only in biological motilities but also in life phenomena at biomembranes. We also clarify that dynamic cooperativity among molecule gives rise to order in molecular dynamics. Hence, dynamic cooperativity is the key mechanism for life phenomena caused by the 'order-from-order' principle at the subcellular level. To produce dynamic cooperativity it is necessary for component molecules or elements to have three states, i.e., inactive (stable) state 0, energized or energy storing (quasi-stable) state 1, and active (unstable) state 2. Each molecule performs elementary cycle 0 yields 1 yields 2 yields 0 repeatedly by using free energy at the molecular level. In a state far from thermodynamic equilibrium dynamic cooperativity is yielded in 2 yields 0 due to a kind of triggering action of neighboring elements and breaks thermodynamic detailed balance. In addition, dynamic cooperativity gives component molecules long-range interactions which depend on the structure of organelles or molecular assemblies. Dynamic cooperativity is able to decrease entropy production and will give a high efficiency in chemo-mechanical conversions. Great progress would be achieved in the understanding of the molecular mechanisms and thermodynamic principles of energy transformations in biological systems, if molecular dynamics during transformation could be directly observed. This is not only because physical changes accompanied by specific movements of macromolecules are essentially involved but also because such molecular movements play a substantial role in energy transformation. Entirely new ideas will be needed for this purpose although high voltage electron microscopy or X-ray diffraction, for instance, is now expected as to be one of the possible tools in the future. Fortunately even at present it is possible to obtain important information on molecular dynamics from biochemical and physiological data, if analyses are properly performed...

Actomyosin↗