Speed Of Contraction Research Articles

Modeling and Simulation of Reinforcement Mechanism in Preventing the Dysfunction of a Bellow-Like Artificial Muscle

Most artificial muscles currently in existence driven by negative pressure are in the form of origami. Their contractions are directly attained by extracting the air internal, and obtaining a differential pressure with the external (0.101[Formula: see text]MPa). During contraction, the artificial muscle simultaneously encounters radial and axial pressures provided by the atmosphere. If the muscle is isotropic, the radial pressure would make the artificial muscle unreliable, which would weaken the muscle’s contraction, including contraction force, ratio, and speed. This paper first introduces the contraction theory and dysfunction of the muscle. Then, an optimization method is proposed as local reinforcement, aiming at the muscle’s dysfunction that may occur during contraction. Then, by analyzing and comparing the optimization effects on the muscle contraction force and deformation with different reinforced regions, the endplates and crests are determined to be appropriate. Subsequently, the deformations of the reinforced regions when stressed are analyzed, and the adequate reinforcement dimensions are confirmed. Finally, the muscle’s model passes the simulation for ensuring its contraction without dysfunction, demonstrating the rationality of the reinforcement method proposed in this paper. Hereby, the goal of reinforcing the muscle’s radial stiffness is achieved, making the artificial muscle generate an optimal contraction performance.

Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation.

Myosin filament-based regulation supplements actin filament-based regulation to control the strength and speed of contraction in heart muscle. In diastole, myosin motors form a folded helical array that inhibits actin interaction; during contraction, they are released from that array. A similar structural transition has been observed in mammalian skeletal muscle, in which cooling below physiological temperature has been shown to reproduce some of the structural features of the activation of myosin filaments during active contraction. Here, we used small-angle x-ray diffraction to characterize the structural changes in the myosin filaments associated with cooling of resting and relaxed trabeculae from the right ventricle of rat hearts from 39°C to 7°C. In intact quiescent trabeculae, cooling disrupted the folded helical conformation of the myosin motors and induced extension of the filament backbone, as observed in the transition from diastole to peak systolic force at 27°C. Demembranation of trabeculae in relaxing conditions induced expansion of the filament lattice, but the structure of the myosin filaments was mostly preserved at 39°C. Cooling of relaxed demembranated trabeculae induced changes in motor conformation and filament structure similar to those observed in intact quiescent trabeculae. Osmotic compression of the filament lattice to restore its spacing to that of intact trabeculae at 39°C stabilized the helical folded state against disruption by cooling. The myosin filament structure and motor conformation of intact trabeculae at 39°C were largely preserved in demembranated trabeculae at 27°C or above in the presence of Dextran, allowing the physiological mechanisms of myosin filament-based regulation to be studied in those conditions.

The Effects of Vertical vs. Horizontal plyometric Training on Sprinting Kinetics in Post Peak Height Female Student Athletes

Plyometric training is a form of jump training that is a useful method to improve sprinting speed due to its propensity to improve neural efficiency, increase joint stiffness and contraction speed. While research has shown that plyometrics can improve jumping and sprinting performance, no studies have compared the effects of different types of plyometric training on sprinting speed in young females. Therefore, the aim of the study was to compare different forms of plyometric training (horizontal and vertical) on sprinting performance in young females. Thirty young females from a private girls college were randomly divided into two groups and trained for seven weeks, twice a week; vertical plyometric (n=11, age 13.50 ± 0.96, peak heigh velocity-PHV: 1.60 ± 1.14), horizontal plyometric training (n=10, 13.40 ± 0.92, PHV:1.60 ± 0.93), and a physical education class as a control (n=15, age, 15.60 ± 0.31, PHV: 2.90 ± 0.55). Participants were tested for sprinting kinetics i.e. force (Fo), maximum power (Pmax), theoretical velocity (Vo), maximal velocity (Vmax), 10, 20 and 30 m split times using a radar gun over 30 m, isometric strength, vertical jump height and horizontal jump distance before and after the intervention. Both the intervention groups significantly improved all performance variables (g= 0.32- 1.30; p<0.05). The vertical group improved all kinetic variables except Fo and Pmax whereas the horizontal group improved all kinetic variables with a greater effect size g= 0.40-1.30. In comparison to the control group, the vertical group significantly improved Vo, Vmax, vertical and broad jump scores whereas the horizontal group significantly improved broad jump and 20 m split time scores (p<0.05). The findings of this study suggest that horizontal plyometric training is more effective in improving sprinting kinetics.

Action and Contribution of the Iliopsoas and Rectus Femoris as Hip Flexor Agonists Examined with Anatomical Analysis.

To evaluate the difference in action between the iliopsoas and rectus femoris muscles in hip flexion by estimating the relative contribution to the maximal hip flexion torque and relative rotation speed. We examined 22 lower limbs of 10 male and 12 female formaldehyde-fixed adult Japanese cadavers. Using morphometric data from cadaver dissections, we calculated the moment arm length and physiological cross-sectional area for each muscle. We considered moment arm length and physiological cross-sectional area as indices of the maximal torque and compared them among the muscles at various hip joint angles. To evaluate the relative rotation speed, we calculated the increase of the hip joint angle for a 1% reduction of the muscle fiber length in each muscle. The rectus femoris contributed approximately 2/3 to the flexion torque in mild flexion up to 60°, whereas the iliopsoas contribution increased sharply beyond 60°. The relative iliopsoas rotation speed was 2.5- to 3-times higher than that of the rectus femoris in mild flexion up to 60° under the specific condition that each muscle had the same muscle contraction speed. We found that the iliopsoas served as a rapid flexor, while the rectus femoris was a powerful flexor.

Sports Science Teaching of Athletics Based on Nonlinear Mathematical Equation

Abstract To study the teaching of sports science in athletics, this paper adopts the method of a nonlinear mathematical equation, According to the explosive power = force * speed and hill force speed equation, the best matching value between the load weight and the muscle contraction speed when the athlete reaches the maximum explosive power is obtained by the mathematical method, to achieve the objective of quantifying and scientifying the maximum explosive power training method according to the individual ability of the athlete. The results show that the training intensity is slightly lower than the optimal strength load (about 30%F0) and faster than the optimal movement speed. Jumping events adopt load weight higher than the optimal load to 50% F0 and load intensity slightly slower than the optimal speed combination for training; Conclusion: According to the characteristics of track and field events, this paper discusses the application of the research results in the training of athletes’ explosive development in different track and field events, to achieve better training effect and improve students’ athletic ability.

Lack of increased rate of force development after strength training is explained by specific neural, not muscular, motor unit adaptations.

Although maximal force increases following short-term isometric strength training, the rate of force development (RFD) may remain relatively unaffected. The underlying neural and muscular mechanisms during rapid contractions after strength training are largely unknown. Since strength training increases the neural drive to muscles, it may be hypothesized that there are distinct neural or muscular adaptations determining the change in RFD independently of an increase in maximal force. Therefore, we examined motor unit population data acquired from surface electromyography during the rapid generation of force before and after 4 wk of strength training. We observed that strength training did not change the RFD because it did not influence the number of motor units recruited per second or their initial discharge rate during rapid contractions. Although strength training did not change motoneuron behavior in the force increase phase of rapid contractions, it increased the discharge rate of motoneurons (by ∼4 spikes/s) when reaching the plateau phase (∼150 ms) of the rapid contractions, determining an increase in maximal force production. Computer simulations with a motor unit model that included neural and muscular properties, closely matched the experimental observations and demonstrated that the lack of change in RFD following training is primarily mediated by an unchanged maximal recruitment speed of motoneurons. These results demonstrate that maximal force and contraction speed are determined by different adaptations in motoneuron behavior following strength training and indicate that increases in the recruitment speed of motoneurons are required to evoke training-induced increases in RFD.NEW & NOTEWORTHY Although maximal force increases with strength training, the rate of force development may remain unaffected. For the first time, we associated motor unit population behavior during rapid force contractions before and after a 4-wk isometric strength training intervention. We found that strength training combined with slow and rapid contractions does not change rate of force development. The specific mechanisms include similar discharge rate during the initial phase of contraction and similar recruitment speed of motoneurons.

Abstract 14330: Contraction-Relaxation Coupling is Unaltered by Heart Failure Status in Human Myocardium

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether these phases are linked in human myocardium is not well understood. Prior investigations have shown that the structural and biochemical myocardial remodeling secondary to exercise training and/or myocardial infarction does not disrupt contraction-relaxation (CR) coupling in the canine model system. In addition, in a wide variety of murine transgenic models targeting EC coupling, the coupling between contraction and relaxation was unaltered. Given the vast differences between inbred animal models and the human population, we investigated whether contraction and relaxation are also coupled in human myocardium, and if so, whether that coupling is affected by heart failure disease status. We retrospectively analyzed data from contractility measurements taken under conditions closely mimicking those in vivo and calculated the correlation between the maximal speed of contraction and the maximal speed of relaxation in human ventricular multicellular preparations. We categorized our data based on heart failure status as follows: non-heart failure, heart failure with ischemic cardiomyopathy, or heart failure with non-ischemic cardiomyopathy. In every case isolated right ventricular trabeculae and/or left ventricular trabeculae (n=53 subjects LV and RV analyzed, 38 subjects only LV, 27 subjects only RV) were isolated from freshly explanted human hearts. Multicellular preparations were then electrically paced at different muscle lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were very tightly linearly correlated regardless of disease category (typical R 2 of >0.98). While the mechanism governing this coupling is unknown, based on data form this study and past studies, we posit that CR-coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere at the basis of cross-bridge cycling.

Quantification of Gastric Contractions Using MRI with a Natural Contrast Agent.

Gastric motility has an essential role in mixing and the breakdown of ingested food. It can affect the digestion process and the efficacy of the orally administered drugs. There are several methods to image, measure, and quantify gastric motility. MRI has been shown to be a suitable non-invasive method for gastric motility imaging. However, in most studies, gadolinium-based agents have been used as an oral contrast agent, making it less desirable for general usage. In this study, MRI scans were performed on 4 healthy volunteers, where pineapple juice was used as a natural contrast agent for imaging gastric motility. A novel method was developed to automatically estimate a curved centerline of the stomach. The centerline was used as a reference to quantify contraction magnitudes. The results were visualized as contraction magnitude-maps. The mean speed of each contraction wave on the lesser and greater curvatures of the stomach was calculated, and the variation of the speeds in 4 regions of the stomach were quantified. There were 3-4 contraction waves simultaneously present in the stomach for all cases. The mean speed of all contractions was 2.4±0.9 mm/s, and was in agreement with previous gastric motility studies. The propagation speed of the contractions in the greater curvature was higher in comparison to the lesser curvature (2.9±0.8 vs 1.9±0.5 mm/s); however, the speeds were more similar near to the pylorus. This study shows the feasibility of using pineapple juice as a natural oral contrast agent for the MRI measurements of gastric motility. Also, it demonstrated the viability of the proposed method for automatic curved centerline estimation, which enables practical clinical translation.Clinical Relevance- MRI is able to non-invasively provide dynamic images of the contraction patterns of the stomach, providing a novel clinical tool for assessing functional motility disorders. The use of a natural oral contrast agent such as pineapple juice, as opposed to a gadolinium-based contrast agent, makes MRI more widely accessible. Our semi-automated methods for quantifying contraction magnitude and speed will streamline analysis and clinical diagnosis.

Thrust-back: a new technique to augment gains in power and power endurance

Background: Speed-oriented power training with light intensities permits rapid acceleration at the beginning of each concentric phase, but necessitates significant deceleration in the later concentric phase to halt the motion. Force exertion and speed of muscle contraction are therefore delimited. To improve the concentric effort, ballistic actions using a Smith machine have been recommended (bench press throws and squat jumps etc). Typical Smith machines however allow vertical pushing exercises only. Hence, a new technique that mimics ballistic actions needs to be developed. In this study, an alternative technique, described as “thrust-back” has been introduced, where the spotter’s hands, rather than the lifter, halt the concentric motion. The effectiveness of thrust-back applied during fast bench press training on concentric velocity as well as gains in 1RM strength, power and power endurance was examined. Methods: Seventeen university students (12 males and 5 females), who abstained from chest exercises for 3~36 months, performed 15 repetitions of fast bench press at 30% 1RM with and without (control) thrust-back. Peak and mean concentric bar velocities were calculated using a string potentiometer. Subjects were then divided into two groups to undergo 8 weeks (16 sessions) of fast bench press training at 30% 1RM (15 repetitions×4~6sets) with or without thrust-back. One-RM, power and power endurance were evaluated before and after the training. Power and power endurance were estimated via the bar flight distances achieved during 20 repetitions of bench press throws at 30% 1RM on a Smith machine. Results: Thrust-back produced greater peak (up to +13%, P<0.001) and mean (up to +10%, P=0.026) concentric velocities than the control. After 8 weeks of implementation, the thrust-back training resulted in similar 1RM improvement to that of the control (+12.9 vs. +6.4%, P<0.001), but yielded greater improvements in the bar flight distances than the control (+13~37% vs. +4~13%, P=0.027). Moreover, the decline in the bar flight distances across 20 repetitions of bench press throws was attenuated after the thrust-back training (P=0.012), while the declining patter remained similar after the control training. Discussion: The augmented concentric velocity (and effort) via thrust-back technique did not magnify 1RM strength gain compared to the control training, however was successfully translated into greater gains in power and power endurance. When Smith machines are not available or not suited to perform the intended exercises, then thrust-back technique may become an alternative strategy since it can be applied to various exercise types. The authors declare no conflict of interest.

Enhanced Store-Operated Ca2+ Signal of Small Intestinal Smooth Muscle Cells Accelerates Small Bowel Transit Speed in Type 1 Diabetic Mouse.

Aims: The underlying mechanism of diabetic enteropathy, a common complication of type 1 diabetes, remains unclear. Store-operated Ca2+ entry (SOCE) is a ubiquitous type of Ca2+ influx involved in various cellular functions. Here, we show that SOCE-related stromal interaction molecule 1 (STIM1) and Orai1 participate in inappropriate cellular Ca2+ homeostasis, augmenting agonist-induced small intestinal smooth muscle contraction and small bowel transit speed in a mouse model of type 1 diabetes.Methods and Results: We used small interfering (si)RNA to suppress STIM1 and Orai1 proteins, and employed intracellular Ca2+, small intestinal contraction and intestinal transit speed measurement to investigate the functional change. We found that SOCE activity and Orai1 and STIM1 expression levels of small intestinal smooth muscle were significantly increased in cells cultured in high glucose medium or in diabetic mice. Gastrointestinal transit speed and SOCE-mediated contractions were markedly increased in diabetic mice; Knocking down Orai1 or STIM1 with siRNA rescued both alterations in diabetic mice. However, the Orai1-large conductance Ca2+-activated K+ (BKCa) channel interaction was decreased in diabetic mice, and suppressing Orai1 expression or inhibiting the BKCa channel increased agonist-induced small intestinal contractions in normal mice.Conclusion: We concluded that the increased SOCE caused by excessive STIM1 and Orai1 expression and decreased Orai1-BKCa interaction augmented small intestinal smooth muscle contraction and accelerated small bowel transit speed in diabetic mice. This finding demonstrates a pathological role for SOCE in diabetic enteropathy and provides a potential therapeutic target for diabetic enteropathy.

Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model.

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE.

Enhancement of engineered cardiac tissues by promotion of hiPSC-cardiomyocyte proliferation

Abstract Background/Introduction Cardiac tissue engineering is a promising strategy to generate human cardiac tissues for modelling cardiac diseases, screening for therapeutic drugs, and repairing the injured heart. Yet, several issues remain to be resolved including the generation of tissues with high cardiomyocyte density. Purpose Determining the effects of the induction of human-induced pluripotent stem cell-derived (hiPSC) cardiomyocyte proliferation post-fabrication. Methods hiPSCs were differentiated into cardiomyocytes, embedded with or without CHIR990121 at three concentrations in a collagen pre-gel, and cast. The engineered cardiac tissues were then cultured in the absence or presence of CHIR99021 for up to 35 days. Hydrogels and engineered cardiac tissues were analysed utilizing rheology and assays to determine viability, proliferation, calcium flow, and contractility. Results Here, we show that the integration of CHIR99021 in collagen I hydrogels promotes proliferation of hiPSC-cardiomyocytes post-fabrication improving contractility of and calcium flow in engineered cardiac tissues. Presence of CHIR99021 has no effect on the gelation kinetic or the mechanical properties of collagen I hydrogels. Analysis of cell density and proliferation based on Ki-67 staining indicates that integration of CHIR99021 together with external CHIR99021 stimulation increases hiPSC-cardiomyocyte number by ∼2-fold within 7 days post-fabrication. Analysis of the contractility of engineered cardiac tissues after another 3 days in the absence of external CHIR99021 shows that CHIR99021-induced hiPSC-cardiomyocyte proliferation results in synchronized calcium flow, rhythmic beating, increases speed of contraction and contraction amplitude, and reduces peak-to-peak time. The CHIR99021-stimulated engineered cardiac tissues exhibited spontaneous rhythmic contractions for at least 35 days. Conclusion Collectively, our data demonstrate the potential of induced cardiomyocyte proliferation to enhance engineered cardiac tissues by increasing cardiomyocyte density and reducing arrhythmia. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Spleen Contraction During Sudden Eupneic Hypoxia Elevates Hemoglobin Concentration.

The spleen contracts progressively during moderate normobaric hypoxia exposure of 20 min, which elevates hemoglobin concentration (Hb). However, acute hypoxia exposure could be shorter and more severe when oxygen systems fail during, e.g., high-altitude sky diving, aircraft cabin pressure drop, balloon flights, extreme altitude climbing, and in some maladies. We aimed to evaluate the speed and magnitude of spleen contraction during short exposure to extreme eupneic hypoxia and its subsequent recovery on oxygen. Eight female and seven male volunteers were exposed to normobaric hypoxia (10% oxygen) for 10 min during sitting rest, followed by 10 min on 100% oxygen. Heart rate (HR), arterial oxygen saturation (SpO2), and mean arterial blood pressure (MAP) were measured continuously. The spleen was measured via ultrasonic imaging every minute for volume calculations, and venous blood samples were drawn before and after exposure for hemoglobin concentration (Hb). Mean (SD) spleen volume was 279 (115) mL before exposure, 219 (75) mL (21% reduction; P = 0.005) at 3 min of exposure, and 201 (93) mL after 10 min exposure to hypoxia (28% reduction; P < 0.001). Hb was 138.8 (7.6) g·L−1 before and 142.9 (8.1) g·L−1 after 10 min of exposure (2.9% increase; P < 0.001). SpO2 was 96.4 (1.7)% before exposure and 74.7 (8.4)% during the last minute of exposure (22.5% reduction; P < 0.001). HR increased from 80 (14) to 90 (17) bpm during exposure (12% increase, P < 0.05). MAP remained unchanged. After 10 min recovery on oxygen, values had been restored for spleen volume and Hb, while SpO2 was higher and HR lower compared with before hypoxia exposure. We concluded that acute normobaric hypoxia of only 10 min caused significant spleen volume contraction with Hb increase. This rapid spleen response, evident already after 3 min of exposure, could have a protective effect during sudden exposure to severe hypoxia.

CHIR99021 Promotes hiPSC-Derived Cardiomyocyte Proliferation in Engineered 3D Microtissues.

Cardiac tissue engineering is a promising strategy to generate human cardiac tissues for modeling cardiac diseases, screening for therapeutic drugs, and repairing the injured heart. Yet, several issues remain to be resolved including the generation of tissues with high cardiomyocyte density. Here, it is shown that the integration of the glycogen synthase kinase-3β inhibitor CHIR99021 in collagen I hydrogels promotes proliferation of human-induced pluripotent stem cell-derived (hiPSC) cardiomyocytes post-fabrication improving contractility of and calcium flow in engineered 3D cardiac microtissues. CHIR99021 has no effect on the gelation kinetics or the mechanical properties of collagen I hydrogels. Analysis of cell density and proliferation based on Ki-67 staining indicates that integration of CHIR99021 together with external CHIR99021 stimulation increases hiPSC-cardiomyocyte number by ≈2-fold within 7 d post-fabrication. Analysis of the contractility of engineered cardiac tissues after another 3 d in the absence of external CHIR99021 shows that CHIR99021-induced hiPSC-cardiomyocyte proliferation results in synchronized calcium flow, rhythmic beating, increased speed of contraction and contraction amplitude, and reduced peak-to-peak time. The CHIR99021-stimulated engineered cardiac microtissues exhibit spontaneous rhythmic contractions for at least 35 d. Collectively, the data demonstrate the potential of induced cardiomyocyte proliferation to enhance engineered cardiac microtissues by increasing cardiomyocyte density.

Pain-induced changes in motor unit discharge depend on recruitment threshold and contraction speed.

At high forces, the discharge rates of lower- and higher-threshold motor units (MU) are influenced in a different way by muscle pain. These differential effects may be particularly important for performing contractions at different speeds since the proportion of lower- and higher-threshold MUs recruited varies with contraction velocity. We investigated whether MU discharge and recruitment strategies are differentially affected by pain depending on their recruitment threshold (RT), across a range of contraction speeds. Participants performed ankle dorsiflexion sinusoidal-isometric contractions at two frequencies (0.25 and 1 Hz) and two modulation amplitudes [5% and 10% of the maximum voluntary contraction (MVC)] with a mean target torque of 20%MVC. High-density surface electromyography recordings from the tibialis anterior muscle were decomposed and the same MUs were tracked across painful (hypertonic saline injection) and nonpainful conditions. Torque variability, mean discharge rate (MDR), DR variability (DRvar), RT, and the delay between the cumulative spike train and the resultant torque output (neuromechanical delay, NMD) were assessed. The average RT was greater at faster contraction velocities (P = 0.01) but was not affected by pain. At the fastest contraction speed, torque variability and DRvar were reduced (P < 0.05) and MDR was maintained. Conversely, MDR decreased and DRvar and NMD increased significantly during pain at slow contraction speeds (P < 0.05). These results show that reductions in contraction amplitude and increased recruitment of higher-threshold MUs at fast contraction speeds appear to compensate for the inhibitory effect of nociceptive inputs on lower-threshold MUs, allowing the exertion of fast submaximal contractions during pain.NEW & NOTEWORTHY Pain induces changes in motor performance, motor unit recruitment, and rate coding behavior that varies across different contraction speeds. Here we show that that pain reduces motor unit discharge rate and prolongs the neuromechanical delay at slow contraction speeds only. This new evidence suggests that there are differential nociceptive inhibitory effects across the motor unit pool, which allows fast submaximal contractions to be exerted despite the presence of pain.

Identification of a novel distension-evoked motility pattern in the mouse uterus.

The dynamic changes in uterine contractility in response to distension are incompletely understood. Rhythmic, propagating contractions of nonpregnant uterine smooth muscle occur in the absence of nerve activity (i.e., myogenic), events that decline during pregnancy and reemerge at parturition. We therefore sought to determine how myogenic contractions of the nonpregnant uterus are affected by distension, which might provide mechanistic clues underlying distension-associated uterine conditions such as preterm birth. Uteri isolated from nulliparous adult female mice in proestrus were video imaged to generate spatiotemporal maps, and myoelectrical activity simultaneously recorded using extracellular suction electrodes. Motility patterns were examined under basal conditions and following ramped intraluminal distension with fluid to 5 and 10 cmH2O. Intraluminal distension caused pressure-dependent changes in the frequency, amplitude, propagation speed, and directionality of uterine contractions, which reversed upon pressure release. Altered burst durations of underlying smooth muscle myoelectric events were concurrently observed, although action potential spike intervals were unchanged. Voltage-gated sodium channel blockade [tetrodotoxin (TTX); 0.6 µM] attenuated both the amplitude of contractions and burst duration of action potentials, whereas all activity was abolished by L-type calcium channel blockade (nifedipine; 1 µM). These data suggest that myogenic motility patterns of the nonpregnant mouse uterus are sensitive to changes in intraluminal pressure and, at high pressures, may be modulated by voltage-gated sodium channel activity. Future studies may investigate whether similar distension-evoked changes occur in the pregnant uterus and the possible pathophysiological role of such activity in the development of preterm birth.

Effective Stimulation Type and Waveform for Force Control of the Motor Unit System: Implications for Intraspinal Microstimulation.

The input–output properties of spinal motoneurons and muscle fibers comprising motor units are highly non-linear. The goal of this study was to investigate the stimulation type (continuous versus discrete) and waveform (linear versus non-linear) controlling force production at the motor unit level under intraspinal microstimulation. We constructed a physiological model of the motor unit with computer software enabling virtual experiments on single motor units under a wide range of input conditions, including intracellular and synaptic stimulation of the motoneuron and variation in the muscle length under neuromodulatory inputs originating from the brainstem. Continuous current intensity and impulse current frequency waveforms were inversely estimated such that the motor unit could linearly develop and relax the muscle force within a broad range of contraction speeds and levels during isometric contraction at various muscle lengths. Under both continuous and discrete stimulation, the stimulation waveform non-linearity increased with increasing speed and level of force production and with decreasing muscle length. Only discrete stimulation could control force relaxation at all muscle lengths. In contrast, continuous stimulation could not control force relaxation at high contraction levels in shorter-than-optimal muscles due to persistent inward current saturation on the motoneuron dendrites. These results indicate that non-linear adjustment of the stimulation waveform is more effective in regard to varying the force profile and muscle length and that the discrete stimulation protocol is a more robust approach for designing stimulation patterns aimed at neural interfaces for precise movement control under pathological conditions.

Thermal Sensitivity of Axolotl Feeding Behaviors.

Musculoskeletal movement results from muscle contractions, recoil of elastic tendons, aponeuroses, and ligaments, or combinations thereof. Muscular and elastic contributions can vary both across behaviors and with changes in temperature. Skeletal muscles reach peak contraction speed at a temperature optimum with performance declining away from that optimum by approximately 50% per 10°C, following the Q10 principle. Elastic recoil action, however, is less temperature sensitive. We subjected Axolotls (Ambystoma mexicanum) to changes from warm (23°C), via medium (14°C), to cold (6°C) temperature across most of their thermal tolerance range, and recorded jaw kinematics during feeding on crickets. We sought to determine if suction feeding strikes and food processing chews involve elastic mechanisms and, specifically, if muscular versus elastic contribution vary with temperature for gape opening and closing. Measurements of peak and mean speed for gape opening and closing during strikes and chews across temperature treatments were compared with Q10-based predictions. We found that strike gape speed decreased significantly from warm and medium to cold treatments, indicating low thermal robustness, and no performance-enhancement due to elastic recoil. For chews, peak, and mean gape closing speeds, as well as peak gape opening speed, also decreased significantly from warm to cold treatments. However, peak gape opening and closing speeds for chews showed performance-enhancement, consistent with a previously demonstrated presence of elastic action in the Axolotl jaw system. Our results add to a relatively small body of evidence suggesting that elastic recoil plays significant roles in aquatic vertebrate feeding systems, and in cyclic food processing mechanisms.

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.

Mutations in myosin S2 alter cardiac myosin-binding protein-C interaction in hypertrophic cardiomyopathy in a phosphorylation-dependent manner

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder primarily caused by mutations in the β-myosin heavy-chain gene. The proximal subfragment 2 region (S2), 126 amino acids of myosin, binds with the C0-C2 region of cardiac myosin-binding protein-C to regulate cardiac muscle contractility in a manner dependent on PKA-mediated phosphorylation. However, it is unknown if HCM-associated mutations within S2 dysregulate actomyosin dynamics by disrupting its interaction with C0-C2, ultimately leading to HCM. Herein, we study three S2 mutations known to cause HCM: R870H, E924K, and E930Δ. First, experiments using recombinant proteins, solid-phase binding, and isothermal titrating calorimetry assays independently revealed that mutant S2 proteins displayed significantly reduced binding with C0-C2. In addition, CD revealed greater instability of the coiled-coil structure in mutant S2 proteins compared with S2Wt proteins. Second, mutant S2 exhibited 5-fold greater affinity for PKA-treated C0-C2 proteins. Third, skinned papillary muscle fibers treated with mutant S2 proteins showed no change in the rate of force redevelopment as a measure of actin–myosin cross-bridge kinetics, whereas S2Wt showed increased the rate of force redevelopment. In summary, S2 and C0-C2 interaction mediated by phosphorylation is altered by mutations in S2, which augment the speed and force of contraction observed in HCM. Modulating this interaction could be a potential strategy to treat HCM in the future.