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.

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.

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.

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.

Spinal and supraspinal control of motor function during maximal eccentric muscle contraction:Effects of resistance training

Neuromuscular activity is suppressed during maximal eccentric(ECC)muscle contraction in untrained subjects owing to attenuated levels of central activation and reduced spinal motor neuron(MN)excitability indicated by reduced electromyography signal amplitude,diminished evoked H-reflex responses,increased autogenic MN inhibition,and decreased excitability in descending corticospinal motor pathways.Maximum ECC muscle force recorded during maximal voluntary contraction can be increased by superimposed electrical muscle stimulation only in untrained individuals and not in trained strength athletes,indicating that the suppression in MN activation is modifiable by resistance training.In support of this notion,maximum ECC muscle strength can be increased by use of heavy-load resistance training owing to a removed or diminished suppression in neuromuscular activity.Prolonged(weeks to months)of heavy-load resistance training results in increased H-reflex and V-wave responses during maximal ECC muscle actions along with marked gains in maximal ECC muscle strength,indicating increased excitability of spinal MNs,decreased presynaptic and/or postsynaptic MN inhibition,and elevated descending motor drive.Notably,the use of supramaximal ECC resistance training can lead to selectively elevated V-wave responses during maximal ECC contraction,demonstrating that adaptive changes in spinal circuitry function and/or gains in descending motor drive can be achieved during maximal ECC contraction in response to heavy-load resistance training.

Experimental gastric dysrhythmias and its correlation with in vivo gastric muscle contractions

瞄准：学习在胃的 dysrhythmias 和在活体内之间的直接关联胃的肌肉音调。方法：五条健康的狗沿着更大的弯曲与 4 个电极被植入，与是的一个紧张计量器(SG ) sutured 平行到远侧的电极(在幽门上面的 2 厘米) 。静脉内的加压素被给导致胃的节律障碍。常规慢波浪和 SG 精力的百分比是计算的。结果：(1 ) 胃的肌电活动(GMA ) 的整齐被减少在期间并且在加压素的注入以后；(2 ) SG 精力显著地在加压素的注入期间被减少；(3 ) 在 SG 精力的减少很好在 GMA 整齐与减小被相关；(4 ) SG 精力否定地与 bradygastria 和 tachygastria 被相关。结论：加压素禁止胃的收缩并且损害胃的慢波浪；胃的 dysrhythmias 与减少的窦肌肉收缩被联系，并且窦运动不足是指示的。

Assessment of Human Skeletal Muscle Contraction and Force by Diffusion Tensor Imaging

We aimed to investigate the association between mobility and skeletal muscle strength by using magnetic resonance diffusion tensor imaging (DTI). This study included 20 healthy male volunteers (mean age, 21.8 ± 1.1 years). The maximum voluntary strength (MVC) of each participant was measured with the ankle joint in plantar and dorsal flexion using an instrument for measuring muscle strength. Moreover, magnetic resonance imaging (MRI) was performed with the ankle joint at rest, in plantar flexion, and in dorsal flexion. For imaging, a 1.5-T MRI device was used, and a diffusion-weighted stimulated echo-planar imaging pulse sequence. Tensor eigenvalues (λ), fractional anisotropy (FA), and the apparent diffusion coefficient (ADC) were calculated from data obtained by DTI. The resulting MRI data were compared to the data on muscle mobility or strength and statistically analyzed. Regarding changes in DTI indices during muscle movements, anisotropy of the tibialis anterior was significantly increased from rest to plantar flexion (P < 0.01), whereas no significant change was observed in dorsal flexion (n.s.). In contrast, the extent of significant changes in anisotropy of the medial gastrocnemius (mGC) and soleus (SOL) was small at plantar flexion (mGC, P < 0.01;SOL, n.s.), whereas the indices were significantly increased at dorsal flexion (P < 0.01). Regarding the correlation between MVC of each skeletal muscle and the DTI indices, FA and λ3 were significantly correlated in movements involving the muscles, whereas no significant correlation was observed in movements not involving them. Changes in intramuscular water molecules by elongation and contraction of the skeletal muscle fibers could be assumed to affect changes in diffusional anisotropy. When muscles contract, the space between myocytes was reduced and they might become increasingly dense. Moreover, diffusional anisotropy increased with increasing MVC, whereas ADC remained unchanged. DTI was suggested to produce measurements similar to the degree of muscle strength.

Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

AIM: To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bebhanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS: Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cisdioxolane (cD), a nonspecific muscarinic agonist, at 10^-8-10^-4mol/L, in the presence of tetrodotoxin (TTX, 10^-7mol/L). Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90min wibh antagonists for M1(pirenzepine), M2(methoctramine) and M3(darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100mg/kg of PTX 5d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS: A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in responsefrom 2.5±0.4g/mm^2 to 1.2±0.4g/mm^2(P<0.05), The doseresponse curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin (M3)>methocramine (M2)>pirenzepine (M1). CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pabhway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the residual contractile response after the treatment with nifedipine, suggests that an additional pathway could mediate the cholinergic contraction. The involvement of more than one muscarinic receptor (functionally predominant type 3 over type 2) also suggests more than one pathway mediating the cholinergic contraction in rat antrum.

YFa and analogs:Investigation of opioid receptors in smooth muscle contraction

AIM:To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS:The effects of YFa and its analogs (D-Ala2) YFa, Y (D-Ala2) GFMKKKFMRF amide and Des-Phe-YGGFMKKKFMR amide in guinea pig ileum (GPI) and mouse vas deferens (MVD) motility were studied using an isolated tissue organ bath system, and morphine and DynA (1-13) served as controls. Acetylcholine was used for muscle stimulation. The observations were validated by specific antagonist pretreatment experiments using naloxonazine, naltrindole and norbinaltor-phimine norBNI. RESULTS:YFa did not demonstrate significant inhibition of GPI muscle contraction as compared with mor-phine (15% vs 62%, P = 0.0002), but moderate inhibition of MVD muscle contraction, indicating the role of κ opioid receptors in the contraction. A moderate inhibition of GPI muscles by (Des-Phe) YFa revealed the role of anti-opiate receptors in the smooth muscle contraction. (D-Ala-2) YFa showed significant inhibition of smooth muscle contraction, indicating the involvement of mainly δ receptors in MVD contraction. These results were supported by specific antagonist pretreatment assays. CONCLUSION:YFa revealed its side-effect-free analgesic properties with regard to arrest of gastroin-testinal transit. The study provides evidences for the involvement of κ and anti-opioid receptors in smooth muscle contraction.

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.

Developmental changes in contraction of gastric smooth muscle cells in rats correlate with their differences in RhoA/ROCK pathway

Previous research has shown that smooth muscle of the stomach undergoes developmental changes in the intracellular regulatory mechanism responsible for the contractile process. Whether these developmental changes relate to differences in the expression and/or activity of the key enzymes regulating smooth muscle contraction has not been previously evaluated. Therefore, we aimed to examine the expression and activation of the small monomeric G protein "Rho A" and Rho kinase(ROCK) as well as their correlation with the contraction of gastric smooth muscle cells(GSMCs) in newborn vs. adult rats. Freshly isolated single GSMCs from Sprague-Dawley rats at 1 week(newborn) and 3 months(adult) of age were used in the study. Protein and m RNA expression levels of both ROCK2 and total Rho A were higher in adult compared to newborn rats. Moreover, acetylcholine(ACh)-induced contractions of GSMCs in adult rats were significantly higher than that in newborn animals. Meanwhile,ROCK and Rho activation was higher in adult stomach cells compared to newborn ones. Pretreatment of GSMCs with Y-27632, the ROCK inhibitor, significantly reduced ACh-induced contraction in both groups of cells and greatly abolished contractile differences. In conclusion, our results indicate that Rho A/ROCK pathway and contraction of stomach muscle cells are under developmental regulation.

Biomechanical response of skeletal muscle to eccentric contractions

The forced lengthening of an activated skeletal muscle has been termed an eccentric contraction(EC).This review highlights the mechanically unique nature of the EC and focuses on the specific disruption of proteins within the cell known as cytoskeletal proteins.The major intermediate filament cytoskeletal protein,desmin,has been the focus of work in this area because changes to desmin occur within minutes of ECs and because desmin has been shown to play both a mechanical and biologic role in a muscle's response to EC.It is hoped that these types of studies will assist in decreasing the incidence of muscle injury in athletes and facilitating the development of new therapies to treat muscle injuries.

Mechanisms of change contraction of function of the muscles <i>in vitro</i>at allergic

In this work, mechanisms of influence of protein sensibility of an organism on contractile function of the isolated skeletal muscles of the mouse—“fast”—musculus extensor digitorum longus, “mixed”—musculus diaphragma and “slow”— musculus soleus are investigated. It is shown that at a protein sensitization all “fast”, “mixed” and “slow” skeletal muscles change the contractile properties. The vector of these changes for muscles with a various phenotypes carries opposite character. Force of the reduction caused carbacholine at a “slow” and “mixed” muscles increase, at “fast”—decreases. A vector of change of force of reduction on carbacholine at protein sensitization at these skeletal muscles correlates with changes of non-quantum secretion acetylcholine in a zone of a trailer plate. Opposite changes of functional properties of “fast” and “mixed” muscles and “slow” muscles of a shin of the mouse at protein sensitization are caused by dynamics cholinoceptive processes of excitation of membrane muscular fibers. It comes out with the assumption, that change of the contraction functions of skeletal muscles at protein sensitization is caused by changes of cholinoceptive processes of excitation of a membrane of muscular fibers, and other changes in system of electro-mechanical interface.

Multifractal analysis of surface EMG signals for assessing muscle fatigue during static contractions

This study is aimed at assessing muscle fatigue during a static contraction using multifractal analysis and found that the surface electromyographic (SEMG) signals characterized multifractality during a static contraction. By applying the method of direct determination of the f(α) singularity spectrum, the area of the multifractal spectrum of the SEMG signals was computed. The results showed that the spectrum area significantly increased during muscle fatigue. Therefore the area could be used as an assessor of muscle fatigue. Compared with the median frequency (MDF)―the most popular indicator of muscle fatigue, the spectrum area presented here showed higher sensitivity during a static contraction. So the singularity spectrum area is considered to be a more effective indicator than the MDF for estimating muscle fatigue.

Effect of the ginsenoside Rb1 on the spontaneous contraction of intestinal smooth muscle in mice

AIM: To investigate the effect and the possible mechanism of ginsenoside Rb1 on small intestinal smooth muscle motility in mice. METHODS: Intestinal smooth muscle strips were isolated from male ICR mice (5 wk old), and the effect of ginsenoside Rb1 on spontaneous contraction was recorded with an electrophysiolograph. The effect of ginsenoside Rb1 on ion channel currents, including the voltage-gated K + channel current (IK V ), calcium-activated potassium channel currents (IK Ca ), spontaneous transient outward currents and ATP-sensitive potassium channel current (IK ATP ), was recorded on freshly isolated single cells using the whole-cell patch clamp technique. RESULTS: Ginsenoside Rb1 dose-dependently inhibited the spontaneous contraction of intestinal smooth muscle by 21.15% ± 3.31%, 42.03% ± 8.23% and 67.23% ± 5.63% at concentrations of 25 μmol/L, 50 μmol/L and 100 μmol/L, respectively (n=5,P<0.05). The inhibitory effect of ginsenoside Rb1 on spontaneous contraction was significantly but incompletely blocked by 10 mmol/L tetraethylammonium or 0.5 mmol/L 4-aminopyridine, respectively (n=5, P<0.05). However, the inhibitory effect of ginsenoside Rb1 on spontaneous contraction was not affected by 10 μmol/L glibenclamide or 0.4 μmol/L tetrodotoxin. At the cell level, ginsenoside Rb1 increased outward potassium currents, and IK V was enhanced from 1137.71 ± 171.62 pA to 1449.73 ± 162.39 pA by 50 μmol/L Rb1 at +60 mV (n=6, P<0.05). Ginsenoside Rb1 increased IK Ca and enhanced the amplitudes of spontaneous transient outward currents from 582.77 ± 179.09 mV to 788.12 ± 278.34 mV (n=5, P<0.05). However, ginsenoside Rb1 (50 μmol/L) had no significant effect on IK ATP (n=3, P<0.05). CONCLUSION: These results suggest that ginsenoside Rb1 has an inhibitory effect on the spontaneous contraction of mouse intestinal smooth muscle mediated by the activation of IK V and IK Ca , but the K ATP channel was not involved in this effect.

sEMG Feature Analysis on Forearm Muscle Fatigue During Isometric Contractions

In order to detect and assess the muscle fatigue state with the surface electromyography(sEMG) characteristic parameters,this paper carried out a series of isometric contraction experiments to induce the fatigue on the forearm muscles from four subjects,and recorded the sEMG signals of the flexor carpi ulnaris.sEMG's median frequency(MDF) and mean frequency(MF) were extracted by short term Fourier transform(STFT),and the root mean square(RMS) of wavelet coefficients in the frequency band of 5—45 Hz was obtained by continuous wavelet transform(CWT).The results demonstrate that both MDF and MF show downward trends within 1 min; however,RMS shows an upward trend within the same time.The three parameters are closely correlated with absolute values of mean correlation coefficients greater than 0.8.It is suggested that the three parameters above can be used as reliable indicators to evaluate the level of muscle fatigue during isometric contractions.

Effect of areca on contraction of colonic muscle strips in rats

AIM: To investigate the effects of areca on the contractileactivity of isolated colonic muscle strips in rats andmechanism involved.METHODS: Each strip (LMPC, longitudinal muscle ofproximal colon; CMPC, circular muscle of proximal colon;LMDC, longitudinal muscle of distal colon; CMlC, circularmuscle of distal colon. ) was suspended in a tissue chambercontaining 5 mL Krebs solution (37 ℃), bubbledcontinuously with 950 mL@ L-1 O2 and 50 mL@ L-1 CO2 . Themean contractile amplitude (A), the resting tension (T),and the contractile frequency (F) were simultaneouslyrecorded on recorders.RESULTS: Arsca dose dependently increased the meancontractile amplitude, the resting tension of proximal anddistal colonic smooth muscle strips in rats ( P ＜ 0.05). Italso partly increased the contractile frequency of colonicsmooth muscle strips in rats ( P ＜ 0.05). The effects werepartly inhibited by atropine (the resting tension of LMPCdecreased from 0. 44 ± 0. 12 to 0. 17 ± 0.03; the restingtension of LMDC decreased from 0.71 ± 0.14 to 0.03 ± 0.01;the mean contractile amplitude of LMPC increased from -45.8 ± 7.2 to -30.5 ± 2.9; the motility index of CMDC decreasedfrom 86.6± 17.3 to 32.8 ± 9.3; P＜ 0.05 vs areca), but theeffects were not inhibited by hexamethonium (P＞ 0.05).CONCLUSION: Areca stimulated the motility of isolatedcolonic smooth muscle strips in rats. The stimulation ofareca might be relevant with M reoeptor partly.

Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms

Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of highfrequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1-and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus(EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca2+-ATPase(SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase(nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated intracellular resting Ca2+ concentration([Ca2+]i) in unloaded soleus muscles. High [Ca2+]i activated calpain-1 which induced a higher degradation of desmin. Desmin degradation may loose connections between adjacent myofibrils and further misaligned Z-disc during repeated tetanic contractions. Passive stretch in unloaded muscle could preserve the stability of sarcoplasmic reticulum Ca2+ release channels by means of keeping nNOS activity, and decrease the enhanced protein level and activity of calpain to control levels in unloaded soleus muscles. Therefore, passive stretch restored normal appearance of Z-disc and resisted in part atrophy of unloaded soleus muscles. The above results indicate that enhanced fatigability of high-frequency tetanic contraction is associated to the alteration in K+ channel characteristics, and elevated SERCA activity and slow to fast transition of myosin heavy chain(MHC) isoforms increases fatigability of intermittent tetanic contraction in atrophic soleus muscle. The sarcomeric damage induced by tetanic contraction can be retarded by stretch in atrophic soleus muscles.

The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction

TRPP2 channel protein belongs to the superfamily of transient receptor potential(TRP) channels and is widely expressed in various tissues, including smooth muscle in digestive gut. Accumulating evidence has demonstrated that TRPP2 can mediate Ca^(2+) release from Ca^(2+) stores. However, the functional role of TRPP2 in gallbladder smooth muscle contraction still remains unclear. In this study, we used Ca^(2+) imaging and tension measurements to test agonist-induced intracellular Ca^(2+) concentration increase and smooth muscle contraction of guinea pig gallbladder, respectively. When TRPP2 protein was knocked down in gallbladder muscle strips from guinea pig, carbachol(CCh)-evoked Ca^(2+) release and extracellular Ca^(2+) influx were reduced significantly, and gallbladder contractions induced by endothelin 1 and cholecystokinin were suppressed markedly as well. CCh-induced gallbladder contraction was markedly suppressed by pretreatment with U73122, which inhibits phospholipase C to terminate inositol 1,4,5-trisphosphate receptor(IP3) production, and 2-aminoethoxydiphenyl borate(2APB), which inhibits IP3 recepor(IP3R) to abolish IP3R-mediated Ca^(2+) release. To confirm the role of Ca^(2+) release in CCh-induced gallbladder contraction, we used thapsigargin(TG)-to deplete Ca^(2+) stores via inhibiting sarco/endoplasmic reticulum Ca^(2+)-ATPase and eliminate the role of store-operated Ca^(2+) entry on the CCh-induced gallbladder contraction. Preincubation with 2 μmol L^(-1) TG significantly decreased the CCh-induced gallbladder contraction. In addition, pretreatments with U73122, 2APB or TG abolished the difference of the CCh-induced gallbladder contraction between TRPP2 knockdown and control groups. We conclude that TRPP2 mediates Ca^(2+) release from intracellular Ca^(2+) stores, and has an essential role in agonist-induced gallbladder muscle contraction.