Effects of adenosine triphosphate concentration on motor force regulation during skeletal muscle contraction

We employ a mechanical model of sarcomere to quantitatively investigate how adenosine triphosphate (ATP) concentration affects motor force regulation during skeletal muscle contraction. Our simulation indicates that there can be negative cross-bridges resisting contraction within the sarcomere and higher ATP concentration would decrease the resistance force from negative cross-bridges by promoting their timely detachment. It is revealed that the motor force is well regulated only when ATP concentration is above a certain level. These predictions may provide insights into the role of ATP in regulating coordination among multiple motors.

Reduction of muscle contraction and pain in electroporation-based treatments:An overview

BACKGROUND In the first studies of electrochemotherapy(ECT),small cutaneous metastases were treated and only mild or moderate pain was observed;therefore,pain was not considered a significant issue.As the procedure began to be applied to larger cutaneous metastases,pain was reported more frequently.For that reason,reduction of both muscle contractions and pain have been investigated over the years.AIM To present an overview of different protocols described in literature that aim to reduce muscle contractions and pain caused by the electroporation(EP)effect in both ECT and irreversible EP treatments.METHODS Thirty-three studies published between January 1999 and November 2020 were included.Different protocol designs and electrode geometries that reduce patient pain and the number of muscle contractions and their intensity were analysed.RESULTS The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions in patients who undergo EP treatments.Moreover,adequate electrode design can decrease EP-related morbidity.Particularly,needle length,diameter and configuration of the distance between the needles can be optimised so that the muscle volume crossed by the current is reduced as much as possible.Bipolar/biphasic pulses with an inadequate pulse length seem to have a less evident effect on the membrane permeability compared with the standard pulse protocol.For that reason,the number of pulses and the voltage amplitude,as well as the pulse duration and frequency,must be chosen so that the dose of delivered energy guarantees EP efficacy.CONCLUSION Pain reduction in EP-based treatments can be achieved by appropriately defining the protocol parameters and electrode design.Most results can be achieved with high frequency and/or bipolar/biphasic pulses.However,the efficacy of these alternative protocols remains a crucial point to be assessed further.

The anatomical,electrophysiological and histological observations of muscle contraction units in rabbits:a new perspective on nerve injury and regeneration

In the conventional view a muscle is composed of intermediate structures before its further division into microscopic muscle fibers.Our experiments in mice have confirmed this intermediate structure is composed of the lamella cluster formed by motor endplates,the innervating nerve branches and the corresponding muscle fibers,which can be viewed as an independent structural and functional unit.In this study,we verified the presence of these muscle construction units in rabbits.The results showed that the muscular branch of the femoral nerve sent out 4–6 nerve branches into the quadriceps and the tibial nerve sent out 4–7 nerve branches into the gastrocnemius.When each nerve branch of the femoral nerve was stimulated from the most lateral to the medial,the contraction of the lateral muscle,intermediate muscle and medial muscle of the quadriceps could be induced by electrically stimulating at least one nerve branch.When stimulating each nerve branch of the tibial nerve from the lateral to the medial,the muscle contraction of the lateral muscle 1,lateral muscle 2,lateral muscle 3 and medial muscle of the gastrocnemius could be induced by electrically stimulating at least one nerve branch.Electrical stimulation of each nerve branch resulted in different electromyographical waves recorded in different muscle subgroups.Hematoxylin-eosin staining showed most of the nerve branches around the neuromuscular junctions consisted of one individual neural tract,a few consisted of two or more neural tracts.The muscles of the lower limb in the rabbit can be subdivided into different muscle subgroups,each innervated by different nerve branches,thereby allowing much more complex muscle activities than traditionally stated.Together,the nerve branches and the innervated muscle subgroups can be viewed as an independent structural and functional unit.This study was approved by the Animal Ethics Committee of Peking University People’s Hospital(approval No.2019 PHE027)on October 20,2019.

Assessment of voluntary rhythmic muscle contraction-induced exercising blood flow variability measured by Doppler ultrasound

Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the ac- tivity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.

Measurement of the exercising blood flow during rhythmical muscle contractions assessed by Doppler ultrasound:Methodological considerations

Given the recent technological developments, ultra-sound Doppler can provide valuable measurements of arterial blood flow with high temporal resolution. In a clinical setting, measurements of hemodynamics is used to monitor, diagnose and manage changes in blood velocity profile for cardiac valve disease, relatively large vessel stenosis and other cardiovascular diseases. In health science and preventive medicine for cardiovascular disease with exercise therapy, evaluation of cardiac and vascular function is a useful indicator not only at rest but also during exercise, leading to improved exercise tolerance as well as physical activity. During exercise, the increase in oxygen uptake (calculated as product of arterial blood flow to the exercising limb and the arteriovenous oxygen difference) is directly proportional to the work performed. The increased oxygen demand is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (major part in the whole exercising muscles) from the blood. Therefore, the determination of the local blood flow dynamics (potential oxygen supply) feeding to rhythmic muscle contractions can contribute to the understanding of the factors limiting the work capacity including, for instance the muscle metabolism, substance utilization and vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound the validity of evaluating blood velocity/flow in the fore- arm or lower limb conduit artery feeding to the mus- cle is demonstrated during rhythmic muscle exercise;however the exercising blood velocity profile (fast Fourier transformation) due to muscle contractions is always seen as a physiological variability or fluctuations in the magnitude in blood velocity due to the spontaneous muscle contraction and relaxation induced changes in force curve intensity. Considering the above mentioned variation in blood velocity in relation to muscle contractions may provide valuable information for evaluating the blood flow dynamics during exercise. This review presents the methodological concept that underlines the methodological considerations for determining the exercising blood velocity/flow in the limb conduit artery in relation the exercise model of dynamic leg exercise assessed by pulsed Doppler ultrasonography.

Mechanochemical model for myosinⅡdimer that can explain the spontaneous oscillatory contraction of muscle

The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myosin II which is a dimeric motor protein with two heads. Taking the two heads of myosin II as an indivisible element and considering the effects of cooperative behavior between the two heads on rate constants in the mechanochemical cycle, the present work proposes the tenstate mechanochemical cycle model for myosin II dimer. The simulations of this model show that the proportion of myosin II in different states periodically changes with time, which results in the sustained oscillations of contractive tension, and serves as the primary factor for SPOC. The good fit of this model to experimental results suggests that the cooperative interaction between the two heads of myosin II dimer may be one of the underlying mechanisms for muscle contraction.

Change in the Muscle Tension of the Shoulder Girdle Muscles in Patients with Spinal Pain, Using the Tone Control® Technique

The aim of the study was to verify the efficacy of the Tone-Control method in inducing a reduction in the tension of the muscles of the shoulder girdle,and therefore a normalisation of posture in the segment.The authors analysed the change in posture,which was related to the muscle tension of the pectoralis major muscle and the trapezius muscle,resulting from the administration of a programme of encoded exercises known as the Tone Control method.The study was conducted on 70 patients with postural back pain,aged between 25 and 81 years and with a mean age of 61.9 years,11 male patients and 59 female patients,who attended group rehabilitation for a minimum of 10 and a maximum of 15 sessions.Acute phase patients,patients on anti-inflammatory pharmacological treatment and patients with hernias or bulging causing thecal sac impingement were excluded from the study.Measurements were taken of the angles of the joints in the scapulohumeral segment during the first and last sessions.The NRS(numeric rating scale)pain scale was administered at the start and end of the cycle of sessions.Conclusions:Patients in the study group experienced improvements in the angle measurements that were proportionally greater than those of the control group,together with a considerable reduction in perceived pain,with an overall improvement in posture and shoulder girdle function.

Registration of the Seated Condylar Position (SCP/CR): Part II: Technique: The Two-Piece Wax Bite Registration

The purpose of this paper is to present the technique for registration of the Seated Condylar Position (SCP)/Centric Relation (CR) position of the condyles: a two-piece wax bite registration with deprogramming and no mandibular manipulation.

Registration of the Seated Condylar Position (SCP/CR): Part I: Rationale

The purpose of this paper is to present the rationale for registration of the Seated Condylar Position (SCP)/Centric Relation (CR) position of the condyles.

Articulated dental cast analysis of asymptomatic and symptomatic populations

Dental instrumentation has long provided insight into the mechanism of musculo-skeletal function of the gnathic system. While large population studies associate dental arch displacement （DAD）, especially laterally, with symptoms, mandibular condyle displacement （CD） resulting from DAD has not been targeted as possibly etiologic in the production of common muscle contraction headache （CMCH） and temporo-mandibular dysfunction （TMD）. The objective was to evaluate the three-dimensional nature of DAD and CD between the seated condylar position （SCP） and the intercuspal position （ICP） and to compare results derived from large deprogrammed asymptomatic and symptomatic populations. A total of 1 192 sets of dental casts collected from asymptomatic and symptomatic populations were articulated in the SCP. The initial occlusal contact, DAD, and condylar displacement were evaluated for frequency, direction, and magnitude of displacement between the SCP and ICP. The data revealed significant displacement between the SCP and ICP of the condyles （displaced most frequently inferior （down） and posterior （distal）） and substantially increased frequency and magnitude of displacement of the dental arches （with posterior premature occlusal contacts, increased overjet, decreased overbite, midline differences, and occlusal classification changes） in symptomatic subjects. These discrepancies were statistically significant and clinically significant. The data support the concept of increased DAD and CD with dysfunction. Transverse condylar displacement, commonly presenting with dental cross bite, may be associated with CMCH and TMD. Displacement of the mandibular condyle may be an etiologic factor in CMCH and dysfunction of the temporo-mandibular joint.

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury （SCI）. To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups： control （no surgical intervention, n = 6）, SCI （SCI only, n = 5）, and electrical simulation （ES; SCI induction followed by ES treatment, n = 10）. A complete spinal cord transection was performed at the 10^th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Com- pared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.

Serum response factor:Look into the gut

Serum response factor(SRF) is a transcription factor that regulates many genes involved in cellular activities such as proliferation,migration,differentiation,angiogenesis,and apoptosis.Although it has only been known for about two decades,SRF has been studied extensively.To date,over a thousand SRF studies have been published,but it still remains a hot topic.Due to its critical role in mesoderm-derived tissues,most of the SRF studies focused on muscle structure/function,cardiovascular development/maintenance,and smooth muscle generation/repair.Recently,SRF has received more attention in the digestive field and several important discoveries have been made.This review will summarize what we have learned about SRF in the gastrointestinal tract and provide insights into possible future directions in this area.

Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle

Overactive bladder(OAB)is the most bothersome symptom in lower urinary tract symptoms(LUTS).Current pharmacologic treatment aims to inhibit detrusor contraction;however,shows unsatisfied efficacy and high discontinuation rate.LIM kinases(LIMKs)promote smooth muscle contraction in the prostate;however,their function in the bladder smooth muscle remains unclear.Here,we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both in vitro and in vivo experiments.Bladder expressions of LIMKs are elevated in OAB rat detrusor tissues.Two LIMK inhibitors,SR7826 and LIMKi3,inhibit contraction of human detrusor strip,and cause actin filament breakdown,as well as cell proliferation reduction in cultured human bladder smooth muscle cells(HBSMCs),paralleled by reduced cofilin phosphorylation.Silencing of LIMK1 and LIMK2 in HBSMCs resulted in breakdown of actin filaments and decreased cell proliferation.Treatment with SR7826 or LIMKi3 decreased micturition frequency and bladder detrusor hypertrophy in rats with bladder outlet obstruction.Our study suggests that LIMKs may promote contraction and proliferation in the bladder smooth muscle,which could be inhibited by small molecule LIMK inhibitors.LIMK inhibitors could be a potential therapeutic strategy for OAB-related LUTS.

Serum from asthmatic rat treated with acupuncture inhibits acetyl-choline-induced contractile responses of airway smooth muscle cells

OBJECTIVE: To investigate the influence of serum from asthmatic rat treated with acupuncture(acupuncture serum) on the contractile responses of airway smooth muscle cells(ASMCs).METHODS: OVA-induced asthmatic rats were subject to acupuncture treatment at the points of Dazhui(GV 14), Fengmen(BL 12), and Feishu(BL 13).The resulting serum was collected, as well as serum from normal animals. Contraction of ASMCs was induced with 10 μM acetylcholine(Ach), and acupuncture serum or normal serum was supplemented 15 min later. The effects of the sera on the changes in cell length, width, and surface areawere monitored in real time via a live cell imaging system.RESULTS: The contraction rates of ASMCs 15 min and 30 min after Ach stimulation reached 38.2% ±3.8% and 49.7% ± 4.6%, both of which were significantly higher than unstimulated control cells(P <0.01). Acupuncture serum at the 1∶100 dosage reduced the contraction rate of ASMCs from 40.1% ±5.1% to 17.6% ± 6.5%(P < 0.01). Thus, the treatment significantly inhibited the Ach-induced contractile responses of ASMCs and yielded a relaxation efficiency of 58%, which was greater than the effects obtained with a 1∶250 dosage. Treatment with acupuncture serum at 1∶500 dosage or normal serum displayed no clear effect of suppressing Ach-induced contraction of ASMCs.CONCLUSION: Our data suggest that acupuncture serum has the effect of inhibiting Ach-induced contraction of ASMCs, thereby promoting relaxation of the cells.

Correlations Between Myoelectric and Hemodynamic Parameters Changes in Biceps Brachii During Sustained Isometric Contraction in Healthy Elderly

Purpose The purpose of the present study was to evaluate the Pearson correlations between hemodynamic parameters obtained with near infrared spectroscopy (NIRS), namely total hemoglobin (tHb) and tissue oxygen index (TOI %), as indica-tors of blood flow and oxygen extraction, and myoelectric parameters obtained with surface multichannel electromyography (sEMG), namely fractal dimension (FD) and conduction velocity (CV) slopes, as descriptors of central and peripheral fatigue, during sustained high level isometric contractions at 60% maximal voluntary contraction (MVC), in elderly subjects. Methods Ten recreationally healthy elderly subjects (age 67.7 ± 4.6 years), 5 males and 5 females, performed one isometric contraction of the elbow flexors at 120° joint angle at 60% of MVC until exhaustion in two subsequent trials 1 week apart, one for the sEMG and the other one for NIRS recordings from the biceps brachii. Results A negative strong Pearson’s correlation between TOI % slope in the functional hyperemic phase (HP) of contrac-tion and a positive correlation between the slope of TOI % recorded during the ischemic phase (IP) and the CV slope were found (r = − 0.76, P < 0.05;r = 0.91, P < 0.01, respectively). A negative strong correlation between tHb IP slope and tHb HP slope and TOI % IP slope and TOI % HP slope (r = − 0.78, P < 0.01;r = − 0.78, P < 0.01, respectively) were also found. No correlation was found between FD slope and hemodynamic parameters (FD slope vs. HP tHb slope, r = − 0.19;FD slope vs. IP tHb slope, r = 0.16;FD slope vs. HP TOI % slope, r = 0.19;FD slope vs. IP TOI % slope, r = 0.27). Conclusion In aged individuals, CV slope correlated with muscle O2 desaturation (TOI %) rather than reduced muscle blood flow (tHb) in the ischemic phase of isometric contraction to exhaustion. No correlations were found between myoelectric manifestations of central fatigue (FD slope) and data obtained by NIRS.

Crk-associated substrate,vascular smooth muscle and hypertension

Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration,hypertrophy and growth.Crk-associated substrate(CAS),the first discovered member of the adapter protein CAS family,has been shown to be a critical cellular component that regulates various smooth muscle functions.In this review,the molecular structure and protein interactions of the CAS family members are summarized.Evidence for the role of CAS in the regu-lation of vascular smooth muscle contractility is pre-sented.Contraction stimulation induces CAS phosphor-ylation on Tyr-410 in arterial smooth muscle,creating the binding site for the Src homology(SH)2/SH3 protein CrkII,which activates neuronal Wiskott-Aldrich syn-drome protein(N-WASP)-mediated actin assembly and force development.The functions of CAS in cell migra-tion,hypertrophy and growth are also summarized.Abelson tyrosine kinase(Abl),c-Src,focal adhesion kinase(FAK),proline-rich tyrosine kinase 2(PYK2),pro-tein tyrosine phosphatase-proline,glutamate,serine and threonine sequence protein(PTP-PEST)and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS.The downstream signaling partners of CAS in the context of cell motility,hyper-trophy,survival and growth are also discussed.These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions.Furthermore,the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

Octopamine modulates the activity of motoneurons related to calling behavior in the gypsy moth Lymantria dispar

A morphofunctional investigation of the different neuronal subpopulations projecting through each of the nerves IV-VI emerging bilaterally from the terminal ab- dominal ganglion （TAG） was correlated with the octopaminergic activity in the ganglion that controls the ovipositor movements associated with caUing behavior in the female gypsy moth Lymantria dispar. Tetramethylrodamine-dextran backfills from nerve stumps resulted in a relatively low number of TAG projections, ranging from 12 to 13 for nerve pair IV, 12 to 14 for nerve pair V, and 8 to 9 for nerve pair VI. Furthermore, as assessed by electrophysiological recordings, a number of fibers within each of these nerves displays spontaneous tonic activity, also when the ganglion is fully disconnected from the ventral nerve cord （VNC）. Octopamine （OA） applications to the TAG strongly enhanced the activ- ity of these nerves, either by increasing the firing rate of a number of spontaneously firing units or by recruiting new ones. This octopaminergic activity affected calling behavior, and specifically the muscle activity leading to cycling extensions of the intersegmental membrane （IM） between segments VIII and IX （ovipositor）. Our results indicate that in the female gypsy moth the octopaminergic neural activity of the TAG is coupled with ex- tensions and retractions oflM for the purpose of releasing pheromone, where motor units innervated by nerve pair IV appear antagonistic with respect to those innervated by nerve pair V.