Isometric Tension Development Research Articles

Gene transfer of human cardiomyopathy β-MyHC mutant R403Q directly alters intact cardiac myocyte calcium homeostasis and causes hyper-contractility.

The R403Q mutation of human cardiac β-myosin heavy chain was the first missense mutation of a sarcomeric protein identified as being causal for hypertrophic cardiomyopathy (HCM), in humans. The direct effect of the R403Q mutant myosin on intracellular calcium homeostasis and contractility is not fully known. Here we have used in vitro gene transfer of the R403Q mutant human β-myosin to study its direct effects on single intact adult cardiac myocyte contractility and calcium homeostasis. In the first experiments, adult cardiac myocytes transduced with the R403Q mutant myosin recombinant viral vectors were compared to myocytes transduced with wild-type human β-myosin (wtMYH7). Efficiency of gene transfer was high in both groups (>98%) and the degree of stoichiometric myofilament incorporation of either the mutant or normal myosin was comparable at ∼40% in quiescent myocytes in primary culture. Sarcomere structure and cellular morphology were unaffected by R403Q myosin expression and myofilament incorporation. Functionally, in electrically paced cardiac myocytes, the R403Q mutant myosin caused a significant increase in intracellular calcium concentration and myocyte hyper-contractility. At the sub-cellular myofilament level, the mutant myosin increased the calcium sensitivity of steady state isometric tension development and increased isometric cross-bridge cycling kinetics. R403Q myocytes became arrhythmic after β-adrenergic stimulation with spontaneous calcium transients and contractions in between electrical stimuli. These results indicate that human R403Q mutant myosin directly alters myofilament function and intracellular calcium cycling. Elevated calcium levels may provide a trigger for the ensuing hypertrophy and susceptibility to arrhythmia that are characteristic of HCM.

A linear systems model of the hydrothermal isometric tension test for assessing collagenous tissue quality

Collagen is the most abundant structural protein in the animal kingdom. Its thermal and thermomechanical properties are often measured using differential scanning calorimetry (DSC) and hydrothermal isometric tension (HIT) tests, respectively. In living tissues, not all collagenous structures (molecules, fibrils, etc.) have the same “quality,” and the heterogeneity among these structures in specific tissues increases with remodeling, aging, and/or disease states. In this paper, first, a peak-fitting analysis is carried out to separate and distinguish the sequential denaturation events in a DSC endotherm, which presumably stem from heterogeneity in the collagen fibrils. The fitting analysis uses one of two functions: a Gaussian function or a function proposed by Miles. The individual endotherms were then convolved with a physics-based parametric function, J(T), proposed by the authors, to model the development of the isometric tension in two stages: 1) tension development due to a sudden increase in conformational entropy as each collagen packet denatures, and 2) additional isometric tension development due to increasing temperature, consistent with rubber thermo-elasticity. The proposed function parameters were then found by fitting to actual HIT curves using a global optimization technique. This model provides a decoupling of the effects of denaturation kinetics and collagen network connectivity and therefore an improved interpretation of HIT test results during the temperature ramp from ambient temperature to 90 °C. The simple model outputs are two parameters, α and β, that have physical meaning and aid in assessing collagenous tissue quality in terms of connectivity and integrity.

Chronic Alcohol Consumption, but not Acute Intoxication, Decreases In Vitro Skeletal Muscle Contractile Function.

Skeletal muscle myopathy accompanying chronic alcohol misuse results in part from a decrease in protein synthesis typically observed in type II-rich muscles that leads to muscle weakness. However, there is a paucity of studies investigating whether the alcohol-induced weakness is intrinsic to the muscle or results primarily from the loss of muscle mass. The present study determines whether acute alcohol (ethanol) intoxication or chronic alcohol consumption decreases the intrinsic contractile function of muscle. Adult male mice were randomly assigned to the chronic alcohol group or given a binge dose of alcohol, and contractile characteristics of the extensor digitorum longus (EDL) were determined in vitro. The weight and physiological cross-sectional area (PCSA) of the EDL were decreased in alcohol-fed mice. Maximum twitch and tetanic tension were also reduced, and there was a downward shift of the absolute force-frequency curve in alcohol-fed mice. However, no alcohol-induced changes were noted when these contractile parameters were normalized for the lower PCSA. Alcohol-fed mice demonstrated greater fatigability, and alcohol-induced decreases in postfatigue specific twitch and tetanic force were independent of a decreased PCSA. Furthermore, postfatigue recovery of muscle force over time was reduced. While alcohol did not alter the content of high-energy phosphates or oxidative phosphorylation complexes I-V, it did reduce myosin heavy chain and troponin-T content. In contrast, contractile properties were not altered when examined 2hours after binge alcohol. These data demonstrate chronic alcohol consumption decreases isometric and tetanic tension development due to a reduction in muscle CSA, whereas the increased fatigability observed was independent of muscle mass. As none of the functional changes were produced by acute alcohol, which produced higher blood alcohol levels than chronic ingestion, our data suggest defects in intrinsic muscle contractility require sustained intake and appear independent of defects in basal energy production.

In vivo treatment with the NF-κB inhibitor ursodeoxycholic acid (UDCA) improves tension development in the isolated mdx costal diaphragm.

Previous experiments have indicated that in vivo administration of ursodeoxycholic acid (UDCA) inhibits nuclear NF-κB activation and has beneficial effects on the structure and function of dystrophic (mdx) muscle. We examined the effect of UDCA on tension development in dystrophic muscle. Isometric tension development was examined in costal diaphragms that were freshly isolated from vehicle and UDCA treated mdx mice. Percent recovery scores were obtained by directly comparing these measurements to those obtained from age-matched nondystrophic mice. Vehicle treated mdx mice exhibited significantly reduced optimal muscle lengths (lo ) and specific twitch and tetanic tensions compared with age-matched nondystrophic mice. UDCA treated preparations exhibited significantly improved tension development with a 33% recovery score. Because UDCA is used in treating certain clinical disorders, these results provide a rationale for human clinical trials using this and related drugs for treatment of Duchenne and related muscular dystrophies.

A Spatially Detailed Model of Isometric Contraction Based on Competitive Binding of Troponin I Explains Cooperative Interactions between Tropomyosin and Crossbridges.

Biophysical models of cardiac tension development provide a succinct representation of our understanding of force generation in the heart. The link between protein kinetics and interactions that gives rise to high cooperativity is not yet fully explained from experiments or previous biophysical models. We propose a biophysical ODE-based representation of cross-bridge (XB), tropomyosin and troponin within a contractile regulatory unit (RU) to investigate the mechanisms behind cooperative activation, as well as the role of cooperativity in dynamic tension generation across different species. The model includes cooperative interactions between regulatory units (RU-RU), between crossbridges (XB-XB), as well more complex interactions between crossbridges and regulatory units (XB-RU interactions). For the steady-state force-calcium relationship, our framework predicts that: (1) XB-RU effects are key in shifting the half-activation value of the force-calcium relationship towards lower [Ca2+], but have only small effects on cooperativity. (2) XB-XB effects approximately double the duty ratio of myosin, but do not significantly affect cooperativity. (3) RU-RU effects derived from the long-range action of tropomyosin are a major factor in cooperative activation, with each additional unblocked RU increasing the rate of additional RU’s unblocking. (4) Myosin affinity for short (1–4 RU) unblocked stretches of actin of is very low, and the resulting suppression of force at low [Ca2+] is a major contributor in the biphasic force-calcium relationship. We also reproduce isometric tension development across mouse, rat and human at physiological temperature and pacing rate, and conclude that species differences require only changes in myosin affinity and troponin I/troponin C affinity. Furthermore, we show that the calcium dependence of the rate of tension redevelopment ktr is explained by transient blocking of RU’s by a temporary decrease in XB-RU effects.

Influence of 120-Day Stimulated Microgravity with Countermeasures on Human Muscle Musculo-Tendinous Stiffness and Contractile Properties

The effect of long-term (120-day) 5 ° head-down tilt (HDT) bed rest with countermeasures (physical training - PT) on the contractile properties and musculo-tendinous stiffness (MTS) of the human triceps surae muscle (TS) was studied in four healthy young women subjects. The training sessions were conducted for 60 min each day for 6-days a week for 14 weeks, and 30-40 min twice a day for 2 weeks under the experiment conditions. The maximal voluntary contraction (MVC), and isometric twitch contraction (P t ), and electrically evoked tetanic tension at 150 impulses. s -1 (Ро), time-to-peak tension (TPT), and half relaxation time (1/2 RT), and total contraction time (TCT) of the twitch were determined. The difference between Ро and MVC expressed as a percentage of Ро and referred to a force deficiency (FD). The MTS was determined according to the electromechanical delay (EMD) value during the explosive voluntary contraction. Surface electrodes sensed electromyographic activity (EMG) in the soleus muscle. A separate timer was used to determine total reaction time (TRT). Pre-motor time (PMT) was taken to be the time interval from the delivery of the signal to change in EMG. Electromechanical delay (EMD) was the time interval between the change in EMG and movement muscle force production. After HDT with PT the TPT, 1/2 RT and TCT of the TS decreased by 4%, 17%, and 19%, respectively. The МVС, Р t , and Р о decreased by 3% (р>0.05), and 14%, and 9%, respectively. The FD had decreased significantly by 10 % (р<0.02). The rate of increase of electrically evoked tetanic did not change significantly during HDT with PT, but the rate of increase in isometric voluntary tension development was increased. The EMD, PMT, and TRT decreased by 12.2% (p<0.05), 5.3% and 7.3% (p<0.01), respectively. The results obtained demonstrate that PT counteracted the negative effect of mechanical unloading, but the total physical load (mainly its intensity) was obviously insufficient to prevent changes to the mechanical properties of the muscular system, although both a nervous and muscular response to PT was observed.

Influence of Simulated Microgravity on Mechanical Properties in the Human Triceps Surae Muscle in vivo

Purpose. The aim of the study was to investigate the effects of a simulated microgravity on the mechanical properties of the human triceps surae (TS) and to assess the effectiveness of physical training (PT) in preventing detrimental effects. Methods. Eight women (aged 26-36 years) underwent 120-d of Bed rest (BR): four underwent Bed rest only (BR group) and four performed PT during this period (BRPT group). The training sessions were conducted for 60 min each day for 6 days a week for 14 weeks, and 30-40 min twice a day for 2 weeks under the experiment conditions. PT was performed over a 4-d cycle: 3-d of training and 1-d of rest. The maximal voluntary contraction (MVC), and isometric twitch contraction (Pt), and electrically evoked tetanic tension at 150 impulses × s -1 (Ро), time-to-peak tension (TPT) of the twitch were determined. The difference between Ро and MVC expressed as a percentage of Ро and referred to a force deficiency (Рd). The MTS was determined according to the electromechanical delay (EMD) value during the explosive voluntary contraction. Surface electrodes sensed electromyographic (EMG) activity in the soleus muscle. Electromechanical delay (EMD) was the time interval between the change in EMG and movement muscle force production. Results. In the BR group, Рt, MVC, and Ро had decreased by 12, 36, 24%, respectively, but Рd had increased by 39%. TPT of the twitch had increased by 14%. The rate of increase of voluntary contractions reduced, but in the electrically evoked contraction no changes were observed. The EMD had increased by 27%. In the BREx group, МVС, Рt, and Ро decreased by 3%, and 14%, and 9%, respectively. TPT had decreased by 4%. The Pd had decreased significantly by 10%. The rate of rise increase of electrically evoked tetanic did not change significantly, but the rate of rise in isometric voluntary tension development was increased. The EMD had decreased by 12%. Conclusion. Unloading decreased function and EMD muscle and, although the PT did attenuate these effects, they did not completely prevent them. It is suggested that the total loading volume (mainly its intensity) was not sufficient to completely prevent alterations in tendon mechanical properties

Low-dose ouabain administration increases Na+,K+-ATPase activity and reduces cardiac force development in rats

BackgroundOuabain is a digitalis compound that inhibits the Na+,K+-ATPase (NKA) activity inducing increment in cardiac force. However, this effect seems to be dose dependent. At low concentration, ouabain can induce an increase of NKA activity. MethodsWe investigated the effects of ouabain administration (25μg/kg/day) for 15 days on cardiac contractility and NKA activity. Blood pressure and left ventricular papillary muscle contraction from placebo and ouabain-treated rats for 15 (OUA15) days were evaluated. Isometric force, post-rest potentiation, positive inotropic intervention produced by isoproterenol, and tetanic tension were measured. The activity and protein expression levels of α1 and α2 isoforms of NKA, sodium calcium exchanger (NCX), sarcoplasmic reticulum calcium ATPase (SERCA2a) and phospholamban (PLB) were also measured. ResultsSystolic and diastolic blood pressures increased after treatment with ouabain. However, isometric tension was reduced in the ouabain treated group. Post-rest potentiation, time parameters, inotropic interventions by isoproterenol and tetanic tension did not change. In the ouabain treated group, NKA activity was increased (Oua 406.16±70.6 vs. CT 282.80±80.5) while protein expression of the α1 isoform of NKA was reduced (Oua 0.97±0.06 vs. CT 0.76±0.05). No changes were observed in protein expression of α2 isoform of NKA, NCX, SERCA2a and PLB. Therefore, although 15-day ouabain treatment increases blood pressure (Oua: 116.4±3 vs. CT: 99.9±3), treatment also reduces isometric tension development (Oua: 0.34±0.14 vs. CT: 0.56±0.22). ConclusionWe suggest that the effects induced by ouabain in the isolated cardiac muscle could be related at least in part, to changes in NKA activity.

Influence of simulated microgravity on mechanical properties in the human triceps surae muscle in vivo. I: Effect of 120 days of bed-rest without physical training on human muscle musculo-tendinous stiffness and contractile properties in young women

PurposeThe aim of this study was to investigate the effect of a 120-day 5° head-down tilt (HDT) bed-rest on the mechanical properties of the human triceps surae muscle in healthy young women subjects.MethodsMeasurements included examination of the properties of maximal voluntary contractions (MVC), twitch contractions (P t) and tetanic contractions (P o). The difference between P o and MVC expressed as a percentage of P o and referred to as force deficiency (P d), was calculated. Electromyographic (EMG) activity in the soleus muscle, electromechanical delay (EMD) and total reaction time (TRT) were also calculated. EMD was the time interval between the change in EMG and the onset of muscle tension. Premotor time (PMT) was taken to be the time interval from the delivery of the signal to change in EMG.ResultsAfter HDT P t, MVC and P o had decreased by 11.5, 36.1, 24.4 %, respectively, P d had increased by 38.8 %. Time-to-peak tension had increased by 13.6 %, but half-relaxation time had decreased by 19.2 %. The rate of rise in isometric voluntary tension development had reduced, but no changes were observed in the electrically evoked contraction. EMD had increased by 27.4 %; PMT and TRT decreased by 21.4, and 13.7 %, respectively.ConclusionThe experimental findings indicated that neural as well as muscle adaptation occurred in response to HDT. EMD is a simple and quick method for evaluation of muscle stiffness changes and can serve as an indicator of the functional condition of the neuromuscular system.

LKB1 and MO25 Demonstrate Significant Interaction with Myofilament Proteins

AMP-activated protein kinase (AMPK) is an energetic regulator in the heart that is activated by alterations in energetic status. AMPK has been shown to alter both metabolic status as well as contractile function in the heart. However to become fully activated, the upstream kinase complex LKB1/MO25/STRAD must phosphorylate AMPK. Recent evidence from our lab clearly illustrates that pre-incubation of demembranated cardiac trabeculae with the LKB1/MO25/STRAD complex (alone) can alter Ca2+-sensitivity of isometric tension development. The mechanism underlying the ability of the LKB1/MO25/STRAD complex to alter myofilament contractility is currently unknown. Accordingly, we hypothesize that the LKB1/MO25/STRAD complex alters myofilament contractility through a direct interaction with myofilament proteins. To test this hypothesis, cardiac trabeculae or cut papillary tissue was harvested from 2 month old male Sprague-Dawley rats following a Krebs-Henselet perfusion. Cardiac trabeculae or papillary strips were demembranated overnight and washed. Myofibrils were isolated and solubilized. Using western blot analysis we show that MO25 remained associated with myofibrillar proteins. Next, we incubated demembranated muscle strips with the LKB1/STRAD/M025 complex (0.02 U/μL) for thirty minutes at 30 C. Following incubation, myofibrils were isolated and solubilized. By western blot analysis, we show a significant increase in the amount of Mo25 as well as LKB1 associated with myofibrillar proteins over un-incubated controls (p=0.0354 and p=<0.0001 for MO25 and LKB1, respectively). We conclude that the myofibrillar proteins can interact with the LKB1/MO25/STRAD complex and that this may underlie the impact of this complex on contractile function. Future studies will be designed to address the physiological relevance of this interaction as well as determine the specific proteins that are interacting with the LKB1/MO25/STRAD complex.

Изменение сократительных свойств трехглавой мышцы голени и электромеханической задержки под влиянием 120-суточной моделируемой микрогравитации с использованием физической тренировки

The effect of a 120-day -5 degrees head-down tilt (HDT) bed rest with countermeasures (physical training) on the mechanical properties of the human triceps surae muscle was studied in four healthy young women aged 28.0. The results showed that the contractile properties of the skeletal muscle studied changed considerably. After HDT without countermeasures the maximal voluntary contraction (MVC) had decreased by 36% (P < 0.05), and the electrically evoked tetanic tension at 150 Hz (P) and isometric twitch contraction (P(t)) had decreased by 24% (P < 0.05) and 12 % (P < 0.05), respectively. Time-to-peak tension (TPT) of the twitch had significantly increased by 14% (P < 0.05), but half-relaxation time (1/2 RT), and total contraction time (TCT) had decreased by 19% (P < 0.05) and 18% (P < 0.05), respectively. The difference between P(o) and MVC expressed as a percentage of P(o) and referred to as force deficiency (P(d)), was also calculated. The P(d) had increased by 40% (P < 0.001). The rate of increase of voluntary contractions calculated according to a relative scale had significantly reduced, but for the electrically evoked contraction no substantial changes were observed. After HDT with countermeasures TPT, 1/2 RT and TCT had decreased by 4%, 7%, 19%, respectively in relation to the control condition. Training had caused a decrease of 3% (P > 0.05) in MVC, and P(t) and in P(o) of 14%, and of 9% (P > 0.05), respectively. The Pd had decreased significantly by 10% (P < 0.05). The rate of increase of electrically evoked tetanic tension did not change significantly during HDT with countermeasures but the rate of increase in isometric voluntary tension development was increased. Physical training provided a reserve of neuromuscular function, which attenuated the effect of bed rest. The experimental findings indicated that neural as well as muscle adaptation occurred in response to HDT with countermeasures.

Mechanism of glabridin‐mediated vasorelaxation of rat main mesenteric artery

Glabridin is one of the major flavonoids found in Glycyrrhiza glabra (licorice) root, an important traditional Chinese medicine, and has been reported to have anti‐atherogenic, anti‐inflammatory and anti‐nephritic properties. Because its acute effect on vascular tone remains unknown, we examined whether glabridin was able to relax rat main mesenteric arteries (RMMA) which had been preconstricted with norepinephrine or U46619. RMMA were mounted on a Mulvany‐Halpern type myograph and isometric tension development was monitored. Glabridin caused a relaxation of preconstricted RMMA at a concentration of as little as 0.1 μM, with a relaxation of ~70% being recorded at a concentration of 30 μM. Relaxation was endothelium‐independent, and was strongly inhibited if the K+ concentration in the bathing solution was raised to 20 mM. Relaxation was also strongly antagonized by inhibiting BKCa channels (with 1 mM TEA), KV channels (with 300 μM 4‐AP), or KATP channels (with 10 μM glibenclamide). These results indicate that glabridin, in a concentration range relevant to that which it may attain in plasma in vivo, induces a vasorelaxation which requires vascular smooth muscle hyperpolarization, possibly mediated by the opening of several types of K+ channels.

Cardiac and skeletal muscle expression of mutant β‐myosin heavy chains, degree of functional impairment and phenotypic heterogeneity in hypertrophic cardiomyopathy

Several mutations in distinct genes, all coding for sarcomeric proteins, have been reported in unrelated kindreds with familial hypertrophic cardiomyopathy (FHC). We have identified nine individuals from three families harboring two distinct mutations in one copy of the β-myosin heavy chain (β-MHC) gene. In this study, the expression of the mutant β-myosin protein isoform, isolated from slow-twitch fibers of skeletal muscle, was demonstrated by Northern and Western blot analysis; this myosin showed a decreased in vitro motility activity and produced a lower actin-activated ATPase activity. Isometric tension, measured in single slow-twitch fibers isolated from the affected individuals, also showed a significant decrease. The degree of impairment of β-myosin function, as well as the loss in isometric tension development, were strictly dependent on the amount of the isoform transcribed from the mutated allele. Interestingly, a strong correlation was also demonstrated between mutant β-myosin content and clinical features of FHC. On the other hand, we were unable to detect any correlation between mutant β-myosin expression and degree of cardiac hypertrophy, thereby strengthening the hypothesis that hypertrophy, one of the hallmarks of FHC, might not necessarily be related to the clinical evolution of this disease. These findings lend support to the notion that additional factors rather than the mutated gene may play a pathogenetic role in cardiac wall thickening, whereas the prognosis appears to be strongly related to the amount of mutant protein.

Role of Vinculin in Ventricular Wall Function

Vinculin (Vcl) is a ubiquitously expressed cytoskeletal protein that localizes at cell adhesion sites in cardiomyocytes. It is a key component in the costamere, which anchors the sarcomeric cytoskeleton to the extracellular matrix via integrins. It has been previously shown that it plays a significant role in mechanotransduction and may affect myocardial mechanical function in a directional-dependent manner. To determine the role of Vcl in regional wall mechanics, cardiac MRI tagging was performed in a cardiac-myocyte-specific vinculin knockout (VclKO) mouse model revealing significant decreases in systolic sheet-normal shear strain (P<0.05) and systolic sheet strain (P<0.05) in KO mice compared with littermate wildtype (WT) controls. In addition, measurements in isolated papillary muscles in heterozygous global vinculin knockout mice showed no difference in isometric fiber tension development consistent with no change in systolic fiber strain in vivo. A finite element model of ventricular mechanics suggested an increase in transverse systolic stress development may explain these observations. We hypothesized that this may be due to an increase in myofilament lattice spacing in the VclKO. Lattice spacing and sarcomere length were measured from optical diffraction patterns generated from FFTs of electron micrographs of VclKO and control hearts. The center-to-center spacing between myosin filaments was 37.6±2.55 nm in barium-contracted VclKO hearts (n=3) compared with 32.9±2.37 nm in WT controls (n=3). In hearts fixed at zero load, this spacing averaged 33.5±1.35 nm in VclKO (n=3) vs. 30.8±0.68 nm in WT (n=3). These results along with sarcomere length measurements suggest Vcl can mediate myofilament architecture and hence directional-dependent systolic force generation. We hypothesize that increasing lattice spacing alters the crossbridge binding angle of myosin heads, increasing the transverse force that they generate. The resulting increase in transverse myofiber stiffness during systole decreases systolic sheet strains.

On the quantitation of an agonist with dual but opposing components of action: Application to vascular endothelial relaxation

In this communication we show that the same principle that underlies the use of the isobolograph for assessing agonist interactions also leads to a method for analyzing the opposing effects of a single agonist. This is the principle of dose equivalence whose application is illustrated here and applied to the endothelium-dependent relaxing component of two putative vasoconstrictor peptides. These studies, employing angiotensin II and endothelin-1, were conducted with isolated preparations of rat aorta that were measured for agonist-induced isometric tension development in both endothelial-denuded and -intact vessels. The dose-effect relation of the relaxing component of each agonist, which should not be calculated from simple effect subtraction, was derived by the method described here.

Static Stretch Training in Conditions of Simulated Microgravity Maintains Contractile Properties of Muscles?

The effect of a 60-day 6° head-down tilt (HDT) of bed rest with and without countermeasures on the mechanical properties of human the triceps surae muscle was studied in 12 healthy young men subjects. One group (n = 6; mean age (30.8 ± 3.1) years) underwent a 60-day HDT and a second group (n = 6; mean age (30.5 ± 1.9) years) underwent HDT with countermeasures (long-term passive stretching). The results shown that the contractile properties of skeletal muscle change considerably. After HDT without countermeasures the maximal voluntary contraction (MVC) declined by 33.5% (p < 0.05), the electrically evoked tetanic tension at 150 Hz (P0) and isometric twitch contraction (Pt) reduced by 18.0% (p < 0.02) and 17.3% (p < 0.05), respectively. Time-to-peak tension (TPT) of the twitch increased by 3.4%, but half-relaxation time (1/2 RT) decreased by 7.2%, and total contraction time (TCT) not significantly increased. The difference between P0 and MVC expressed as a percentage of P0 and referred to as force deficiency (Pd), has also been calculated. The Pd increased by 61% (p < 0.001). The rate of rise of voluntary contractions calculated according to an relative scale significantly reduced, but the electrically evoked contraction no substantial changes were observed. After HDT with long-term passive stretching caused decrease by 43.0% (p < 0.05) in MVC, and Pt, and in P0 by 17.0%, and by 19.4% (p < 0.05), respectively. The Pd increased significantly by 100% (p < 0.001). TPT, and 1/2 RT not change significantly, and TCT of the twitch increased by 6.5%, respectively in relation to the control condition. The rate of rise of electrically evoked tetanic tension did not change significantly during HDT with countermeasures but the rate of rise in on isometric voluntary tension development were decreased. These data indicate that prolonged passive stretching of a single muscle decreases voluntary strength. Thus, the received data specify, that the long passive stretching of a muscle does not find out preventive facilitate contractile properties of the muscular device from negative influences of mechanical unloading. This study presents evidence that prolonged passive muscle stretching can lead to some modification of contraction material behavior. In addition, altered material properties seem to affect proprioceptive feedback and, therefore, the motor unit activation in proportion to the contractile failure.

Succinylcholine activation of human horizontal eye muscles

Succinylcholine (Sch) can induce contracture in slow, multiply innervated muscle fibres of the extraocular muscles in animals of different species. Slow muscle fibres also exist in human eye muscle but their physiological properties have not been studied. Isometric tension development was recorded in the lateral and medial rectus muscles in 12 patients operated under general anaesthesia. A strain gauge probe was attached with 5-0 silk sutures to the muscle tendon. Recordings were made in 12 eye muscles with the tendon attached to the globe and in four muscles detached from the globe. Muscle activation was produced by i.v. injection of Sch at a dose of 0.2-0.3 mg/kg bodyweight. A single injection of Sch induced slow contractures lasting for several minutes. In the muscles attached to the globe, mean maximal isometric tension was 12.2 g in the lateral rectus and 12.8 g in the medial rectus. Similar tension was shown in the muscles detached from the globe. The contracture of eye muscles in response to Sch showed characteristics typical of slow muscle fibre activation in amphibian and avian muscle and confirmed the participation of slow fibre systems in ocular motor control.

Нервно-мышечные ответы трехглавой мышцы голени на продолжительное пассивное растяжение мышц-разгибателей стопы у человека в условиях механической разгрузки

The effect of a 60-day 6 degrees head-down tilt (HDT) of bed rest with and without countermeasures on the mechanical properties of human the triceps surae muscle was studied in 12 healthy young men subjects. One group (n=6; mean age 30.8 +/- 3.1 years) underwent a 60-day HDT and a second group (n=6; mean age 30.5 +/- 1.9 years) underwent HDT with countermeasures (long-term passive stretching). The results showed that the contractile properties of skeletal muscle change considerably. After HDT without countermeasures the maximal voluntary contraction (MVC) declined by 33.5% (P < 0.05), the electrically evoked tetanic tension at 150 Hz (Po) and isometric twitch contraction (Pt) reduced by 18.0% (P < 0.02) and 17.3% (P < 0.05), respectively. Time-to peak tension (TPT) of the twitch increased by 3.4%, but half-relaxation time (1/2 RT) decreased by 7.2%, and total contraction time (TCT) increased not significantly. The difference between Po and MVC expressed as a percentage of Po and referred to as force deficiency (Pd), has also been calculated. The Pd increased by 61% (P < 0.001). The rate of rise of voluntary contractions calculated according to an relative scale significantly reduced, but the electrically evoked contraction no substantial changes were observed. After HDT with long-term passive stretching caused decrease by 43.0% (P < 0.05) in MVC, and Pt and in Po by 17.0%, and by 19.4% (P < 0.05), respectively. The Pd increased significantly by 100% (P < 0.001). TPT, and 1/2 RT not change significantly, and TCT of the twitch increased by 6.5%, respectively in relation to the control condition. The rate of rise of electrically evoked tetanic tension did not change significantly during HDT with countermeasures but the rate of rise in on isometric voluntary tension development were decreased. These data indicate that prolonged passive stretching of a single muscle decreases voluntary strength. Thus, the received data specify, that the long passive stretching of a muscle does not find out preventive facilitate contractile properties of the muscular device from negative influences of mechanical unloading. This study presents evidence that prolonged passive muscle stretching can lead to some modification of contraction material behavior. In addition, altered material properties seem to affect proprioceptive feedback and, therefore, the motor unit activation in proportion to the contractile failure.

Nonlinear Dynamic Modeling of Isometric Force Production in Primate Eye Muscle

Although the oculomotor plant is usually modeled as a linear system, recent studies of ocular motoneuron behavior have drawn attention to the presence of significant nonlinearities. One source of these is the development of muscle force in response to changes in motoneuron firing rate. Here, we attempt to simulate the production of isometric force by the primate lateral rectus muscle in response to electrical stimulation [A. Fuchs and E. Luschei, "Development of isometric tension in simian extraocular muscle," J. Physiol., vol. 219, no. 1, pp. 155-166, 1971] by comparing four different modeling approaches. The data could be well fitted either by parameter estimation for physically based models of force production [J. Bobet, E. R. Gossen, and R. B. Stein, "A comparison of models of force production during stimulated isometric ankle dorsiflexion in humans," IEEE Trans. Neural Syst. Rehabil. Eng., vol. 13, no. 4, pp. 444-451, Dec. 2005; E. Mavritsaki, N. Lepora, J. Porrill, C. H. Yeo, and P. Dean, "Response linearity determined by recruitment strategy in detailed model of nictitating membrane control," Biol. Cybern., vol. 96, no. 1, pp. 39-57, 2007], or by the application of a generic method for nonlinear system identification (the nonlinear autoregressive with exogenous input (NARX) model). These results suggest that nonlinear system identification may be a useful method for modeling more general aspects of muscle function, and provide a basis for distributed models of motor units in extraocular muscle for understanding dynamic oculomotor control. The success of previous linear models points to the potential importance of motor unit recruitment in overcoming nonlinearities in the oculomotor plant.

Synchronous In Situ ATPase Activity, Mechanics, and Ca 2+ Sensitivity of Human and Porcine Myocardium

Flash-frozen myocardium samples provide a valuable means of correlating clinical cardiomyopathies with abnormalities in sarcomeric contractile and biochemical parameters. We examined flash-frozen left-ventricle human cardiomyocyte bundles from healthy donors to determine control parameters for isometric tension ( P o) development and Ca 2+ sensitivity, while simultaneously measuring actomyosin ATPase activity in situ by a fluorimetric technique. P o was 17 kN m −2 and pCa 50% was 5.99 (28°C, I = 130 mM). ATPase activity increased linearly with tension to 132 μM s −1. To determine the influence of flash-freezing, we compared the same parameters in both glycerinated and flash-frozen porcine left-ventricle trabeculae. P o in glycerinated porcine myocardium was 25 kN m −2, and maximum ATPase activity was 183 μM s −1. In flash-frozen porcine myocardium, P o was 16 kN m −2 and maximum ATPase activity was 207 μM s −1. pCa 50% was 5.77 in the glycerinated and 5.83 in the flash-frozen sample. Both passive and active stiffness of flash-frozen porcine myocardium were lower than for glycerinated tissue and similar to the human samples. Although lower stiffness and isometric tension development may indicate flash-freezing impairment of axial force transmission, we cannot exclude variability between samples as the cause. ATPase activity and pCa 50% were unaffected by flash-freezing. The lower ATPase activity measured in human tissue suggests a slower actomyosin turnover by the contractile proteins.