Identification of sequence changes in myosin II that adjust muscle contraction velocity

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj < 0.05) but not with the clade (padj > 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat–human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin–myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate.

Power Amplification Increases With Contraction Velocity During Stretch-Shortening Cycles of Skinned Muscle Fibers

Muscle force, work, and power output during concentric contractions (active muscle shortening) are increased immediately following an eccentric contraction (active muscle lengthening). This increase in performance is known as the stretch-shortening cycle (SSC)-effect. Recent findings demonstrate that the SSC-effect is present in the sarcomere itself. More recently, it has been suggested that cross-bridge (XB) kinetics and non-cross-bridge (non-XB) structures (e.g., titin and nebulin) contribute to the SSC-effect. As XBs and non-XB structures are characterized by a velocity dependence, we investigated the impact of stretch-shortening velocity on the SSC-effect. Accordingly, we performed in vitro isovelocity ramp experiments with varying ramp velocities (30, 60, and 85% of maximum contraction velocity for both stretch and shortening) and constant stretch-shortening magnitudes (17% of the optimum sarcomere length) using single skinned fibers of rat soleus muscles. The different contributions of XB and non-XB structures to force production were identified using the XB-inhibitor Blebbistatin. We show that (i) the SSC-effect is velocity-dependent—since the power output increases with increasing SSC-velocity. (ii) The energy recovery (ratio of elastic energy storage and release in the SSC) is higher in the Blebbistatin condition compared with the control condition. The stored and released energy in the Blebbistatin condition can be explained by the viscoelastic properties of the non-XB structure titin. Consequently, our experimental findings suggest that the energy stored in titin during the eccentric phase contributes to the SSC-effect in a velocity-dependent manner.

Echocardiography in the Assessment of Intraventricular Flows and Pressure Gradients in Obstructive Hypertrophic Cardiomyopathy

Aim To evaluate results of myomectomy by intraventricular pressure gradients (IVPG) and blood flows in patients with obstructive hypertrophic cardiomyopathy (OHCMP).Material and methods The study included a total of 76 subjects, 42 patients with OHCMP (mean age, 39±7 years) and 34 healthy volunteers (mean age, 41±3 years). Prior to and after myomectomy, transthoracic echocardiography was performed and followed by digital image processing and calculation of IVPG and left ventricular (LV) vortex flows. Vector analysis was used to estimate the myocardial displacement rate (V), vortex flows, and LV apex-to-base pressure gradients.Results The study showed a dynamic decrease in the LV apex-to-outflow IVPG by more than 50% and recovery of myocardial contraction velocity in the septal area (р<0.001). The decrease in LV cavity pressure gradient serves as an index for evaluating the effectiveness of OHCMP correction. Myomectomy reduces the load on the myocardium and abolishes mitral valve regurgitation with improvement of LV blood flows as also evidenced by the dynamics of long axis velocity change during the cardiac cycle (dL / dt) and the myocardial contraction velocity (V).Conclusion Effectiveness of the surgical correction of OHCMP is based on the dynamics of myocardial contraction velocities, vortex blood flows, and a decrease in LV apex-to-base IVPG.

Age-Related Changes in Molecular and Whole Muscle Function: Role of Fat Content?

Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p&lt;0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p&lt;0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.

Appendicular Muscle Physiology and Biomechanics in Crocodylus niloticus

Archosaurian reptiles (including living crocodiles and birds) had an explosive diversification of locomotor form and function since the Triassic approximately 250 million years ago. Their limb muscle physiology and biomechanics are pivotal to our understanding of how their diversity and evolution relate to locomotor function. Muscle contraction velocity, force, and power in extinct archosaurs such as early crocodiles, pterosaurs, or non-avian dinosaurs are not available from fossil material, but are needed for biomechanical modeling and simulation. However, an approximation or range of potential parameter values can be obtained by studying extant representatives of the archosaur lineage. Here, we study the physiological performance of three appendicular muscles in Nile crocodiles (Crocodylus niloticus). Nile crocodile musculature showed high power and velocity values—the flexor tibialis internus 4 muscle, a small “hamstring” hip extensor, and knee flexor actively used for terrestrial locomotion, performed particularly well. Our findings demonstrate some physiological differences between muscles, potentially relating to differences in locomotor function, and muscle fiber type composition. By considering these new data from a previously unstudied archosaurian species in light of existing data (e.g., from birds), we can now better bracket estimates of muscle parameters for extinct species and related extant species. Nonetheless, it will be important to consider the potential specialization and physiological variation among muscles, because some archosaurian muscles (such as those with terrestrial locomotor function) may well have close to double the muscle power and contraction velocity capacities of others.

Identifying Predictors of Levator Veli Palatini Muscle Contraction During Speech Using Dynamic Magnetic Resonance Imaging

Purpose The purpose of this study was to identify predictors of levator veli palatini (LVP) muscle shortening and maximum contraction velocity in adults with normal anatomy. Method Twenty-two Caucasian English-speaking adults with normal speech and resonance were recruited. Participants included 11 men and 11 women ( M = 22.8 years, SD = 4.1) with normal anatomy. Static magnetic resonance images were obtained using a three-dimensional static imaging protocol. Midsagittal and oblique coronal planes were established for visualization of the velum and LVP muscle at rest. Dynamic magnetic resonance images were obtained in the oblique coronal plane during production of “ansa.” Amira 6.0.1 Visualization and Volume Modeling Software and MATLAB were used to analyze images and calculate LVP shortening and maximum contraction velocity. Results Significant predictors ( p < .05) of maximum LVP shortening during velopharyngeal closure included mean extravelar length, LVP origin-to-origin distance, velar thickness, pharyngeal depth, and velopharyngeal ratio. Significant predictors ( p < .05) of maximum contraction velocity during velopharyngeal closure included mean extravelar length, intravelar length, LVP origin-to-origin distance, and velar thickness. Conclusions This study identified six velopharyngeal variables that predict LVP muscle function during real-time speech. These predictors should be considered among children and individuals with repaired cleft palate in future studies.

Cardiac contraction velocity has evolved to match heart rate with body size through variation in β-cardiac myosin sequence

Heart rate and the maximum velocity of contraction of striated muscle are inversely related to species size. As mammals evolve to different sizes, adaptations are required such as slower contracting heart and skeletal muscles. Analysis of the motor domain of β-myosin from 67 mammals from two clades identifies 14 sites, out of 800, strongly associated with body mass (p<0.01) but not with the clade (p>0.05). Nine of these sites were mutated in the human β-myosin to make it resemble the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a two fold increase in both motility and in the rate of ADP release from the actin.myosin cross-bridge (the step that limits contraction velocity). Both clades use the same small set of amino acids to adjust contraction velocity, suggesting a limited number of ways in which velocity can be manipulated.

Effect of habitual foot-strike pattern on the gastrocnemius medialis muscle-tendon interaction and muscle force production during running

The interaction between gastrocnemius medialis (GM) muscle and Achilles tendon, i.e., muscle-tendon unit (MTU) interaction, plays an important role in minimizing the metabolic cost of running. Foot-strike pattern (FSP) has been suggested to alter MTU interaction and subsequently the metabolic cost of running. However, metabolic data from experimental studies on FSP are inconsistent, and a comparison of MTU interaction between FSP is still lacking. We, therefore, investigated the effect of habitual rearfoot and mid-/forefoot striking on MTU interaction, ankle joint work, and plantar flexor muscle force production while running at 10 and 14 km/h. GM muscle fascicles of 9 rearfoot and 10 mid-/forefoot strikers were tracked using dynamic ultrasonography during treadmill running. We collected kinetic and kinematic data and used musculoskeletal models to determine joint angles and calculate MTU lengths. In addition, we used dynamic optimization to assess plantar flexor muscle forces. During ground contact, GM fascicle shortening ( P = 0.02) and average contraction velocity ( P = 0.01) were 40–45% greater in rearfoot strikers than mid-/forefoot strikers. Differences in contraction velocity were especially prominent during early ground contact. Moreover, GM ( P = 0.02) muscle force was greater during early ground contact in mid-/forefoot strikers than rearfoot strikers. Interestingly, we did not find differences in stretch or recoil of the series elastic element between FSP. Our results suggest that, for the GM, the reduced muscle energy cost associated with lower fascicle contraction velocity in mid-/forefoot strikers may be counteracted by greater muscle forces during early ground contact. NEW & NOTEWORTHY Kinetic and kinematic differences between foot-strike patterns during running imply (not previously reported) altered muscle-tendon interaction. Here, we studied muscle-tendon interaction using ultrasonography. We found greater fascicle contraction velocities and lower muscle forces in rearfoot compared with mid-/forefoot strikers. Our results suggest that the higher metabolic energy demand due to greater fascicle contraction velocities might offset the lower metabolic energy demand due to lower muscle forces in rearfoot compared with mid-/forefoot strikers.