BACKGROUND & AIMS: :This laboratory has previously demonstrated that shortening of the cell body of a heterotrich ciliate, Blepharisma japonicum, could be induced as a step-down photophobic response. Here, we examined the structure and contractility of the myonemes in detergent-extracted cell models and in isolated cortical fragments. Ultrastructural observation showed that the myoneme was connected to the basal ends of the posterior kinetosomes and constructed a systematic network as a whole. Shortening of the cell model was induced by > 10(-4) M Ca(2+), while the rounded cell model did not re-elongate even when it was washed in a calcium-free solution either with or without addition of ATP. Fluffy fibrils, which were tentatively identified as aggregated bundles of the myonemes, were isolated with the kinetosomal complex and showed calcium-dependent and ATP-independent contraction. The minimum concentration of Ca(2+) required for inducing contraction was at the level of 10(-6) M. These results suggest that the cell body shortening in Blepharisma is caused by the Ca(2+)-dependent contraction of the myonemal network.

背景与目标： : 该实验室先前已证明，可以诱导异纤毛虫 (blenpharisma japonicum) 的细胞体缩短，这是一种降低的疏光反应。在这里，我们检查了去污剂提取的细胞模型和分离的皮质碎片中肌电图的结构和收缩力。超微结构观察表明，肌球蛋白与后运动小体的基底末端相连，并整体构建了系统网络。> 10(-4) M Ca(2) 诱导细胞模型的缩短，而圆形细胞模型即使在有或没有添加ATP的情况下在无钙溶液中洗涤也不会重新伸长。蓬松的原纤维，初步鉴定为肌腱的聚集束，与动蛋白复合物一起分离，并显示出钙依赖性和ATP依赖性收缩。诱导收缩所需的最小Ca(2) 浓度为10(-6) M。这些结果表明，眼睑的细胞体缩短是由肌神经网络的Ca(2) 依赖性收缩引起的。

BACKGROUND & AIMS: :We have used a high-resolution small angle X-ray scattering system, together with a high-performance CCD camera, on the BioCAT beamline at the APS synchrotron radiation facility at the Argonne National Laboratory, to study X-ray interference effects in the meridional reflections generated by the arrays of myosin crossbridges in contracting muscle. These give information about axial movements of the myosin heads during contraction with sub-nanometer resolution. Using whole intact muscle preparations (frog sartorius) we have been able to record the detailed behavior of M3 (the first order meridional reflection from the myosin crossbridges, at 14.56 nm) at each of a number of quick releases of increasing magnitude, on the same specimen, and at the same time make similar measurements on higher order myosin meridional reflections, particularly M6. The latter provides information about the dispersion of lever arm angles of the actin-attached myosin heads. The observations show that in isometric contraction the lever arm angles are dispersed through +/- 20-25 degrees on either side of a mean orientation that is about 60 degrees away from their orientation at the end of the working stroke: and that they move towards that orientation in synchronized fashion, with constant dispersion, during quick releases. The relationship between the shift in the interference fringes (which measures the shift of the myosin heads scattering mass towards the center of the sarcomere, and the changes in the total intensity of the reflections, which measures the changes in the axial profile of the heads, is consistent with the tilting lever arm mechanism of muscle contraction. Significant fixed contributions to the meridional reflections come from unattached myosin heads and from backbone components of the myosin filaments, and the interaction of these with the contributions from actin-attached myosin heads determines the behavior of these reflections.

背景与目标： : 我们在阿贡国家实验室APS同步加速器辐射设施的BioCAT束线上使用了高分辨率小角度x射线散射系统以及高性能CCD相机，研究收缩肌肉中肌球蛋白交叉桥阵列产生的子午反射中的x射线干扰效应。这些以亚纳米分辨率提供了有关收缩过程中肌球蛋白头部轴向运动的信息。使用完整的完整肌肉制剂 (frog sartorius)，我们已经能够记录M3的详细行为 (肌球蛋白横桥的一阶子午反射，在14.56 nm处)，在相同的标本上，同时对高阶肌球蛋白子午反射，特别是m6进行类似的测量。后者提供了有关肌动蛋白附着的肌球蛋白头的杠杆臂角度分散的信息。观察结果表明，在等距收缩中，杠杆臂角在平均方向的两侧分散了20-25度，该方向在工作行程结束时与它们的方向相距约60度: 并且它们以同步方式向该方向移动，并具有恒定的色散，在快速释放期间。干涉条纹的位移 (测量肌球蛋白头部散射质量向肌节中心的位移) 与反射总强度的变化 (测量头部轴向轮廓的变化) 之间的关系，与肌肉收缩的倾斜杠杆臂机制一致。对子午反射的显着固定贡献来自未附着的肌球蛋白头和肌球蛋白细丝的骨干成分，而这些与肌动蛋白附着的肌球蛋白头的贡献的相互作用决定了这些反射的行为。

BACKGROUND & AIMS: :During normal muscle shortening, the myosin heads must undergo many cycles of interaction with the actin filaments sliding past them. It is important to determine what range of configurations is found under these circumstances, and, in terms of the tilting lever arm model, what range of orientations the lever arms undergo. We have studied this using the X-ray interference technique described in the previous article, focusing mainly on the changes in the first order meridional reflection (M3) as compared to isometric. The change in ratio of the heights of the interference peaks indicates how far the mean lever arm angle has moved towards the end of the working stroke; the total intensity change depends on the angle change, on the number of heads now attached at any one time, and on the dispersion of lever arm angles. The latter provides a measure of the distance over which myosin heads remain attached to actin as they go through their working strokes. Surprisingly, the mean position of the attached heads moves only about 1 nm inwards (towards the center of the A-band) at low velocity shortening (around 0.9 T0): their dispersion changes very little. This shows that they must be detaching very early in the working stroke. However, at loads around 0.5 T0, the mean lever arm angle is about half way towards the end of the working stroke, and the dispersion of lever arm angles (with a uniform dispersion) is such as to distribute the heads throughout the whole of the working stroke. At higher velocities of shortening (at 0.3 T0), the mean position shifts further towards the end of the stroke, and the dispersion increases further. The details of the measurements, together with other data on muscle indicate that the force-generating mechanism within the myosin heads must have some unexpected properties.

背景与目标： : 在正常肌肉缩短期间，肌球蛋白头必须经历许多周期的相互作用，肌动蛋白丝滑过它们。重要的是要确定在这些情况下发现什么范围的配置，以及就倾斜杠杆臂模型而言，杠杆臂经历什么范围的取向。我们使用上一篇文章中描述的x射线干涉技术对此进行了研究，主要关注与等距相比，一阶子午反射 (M3) 的变化。干涉峰的高度之比的变化表明平均杠杆臂角度已向工作行程的末端移动了多远; 总强度变化取决于角度变化，现在随时连接的磁头数量以及杠杆臂角度的分散。后者提供了肌球蛋白头在进行工作行程时与肌动蛋白保持附着的距离的量度。令人惊讶的是，在低速缩短 (约0.9 T0) 下，附接的头的平均位置仅向内移动约1 nm (朝向A带的中心): 它们的色散变化很小。这表明它们必须在工作行程的早期就分离。然而，在约0.5 T0的负载下，平均杠杆臂角大约是朝向工作冲程结束的一半，并且杠杆臂角的分散 (具有均匀的分散) 使得头部分布在整个工作冲程中。在较高的缩短速度下 (在0.3 T0)，平均位置进一步移向行程的终点，并且色散进一步增加。测量的细节以及其他有关肌肉的数据表明，肌球蛋白头部内的力产生机制必须具有一些意想不到的特性。

BACKGROUND & AIMS: :Cell-level mechanical and 3D spatial cues are essential to the organization and architecture of new tissues that form during growth, repair or in bioreactors. Fibroblast-seeded 3D collagen constructs have been used as bioartifical extracellular matrix (ECM) providing a 3D environment to embedded resident cells. As cells attach to scaffold fibrils, they generate quantifiable contractile forces which depend on cell type, cell attachment, cell density, growth factors, and matrix stiffness. The aim of this study was to quantify the cytomechanical and molecular responses of human dermal (HDF) and neonatal foreskin fibroblasts (HNFF) seeded in constructs of increased stiffness. We also tested the effect of blocking early attachment using serum starvation on these outputs. Constructs were placed under uniaxial strains of 0-10% to increase scaffold stiffness, prior to gel contraction, and force generation was monitored using a tensional culture force monitor (t-CFM). Increased matrix stiffness reduced generation of quantifiable cellular force (up to 70%) over 24 h in both cell types and delayed the onset of measurable contraction (upto sevenfold). The delay of measurable force generation was cell lineage dependent but not FCS dependent. Gene expression of MMP-2, TIMP-2, and collagen type III expression in HDFs were significantly upregulated in constructs of increased stiffness. HNFFs did not show any significant changes in these gene expressions indicating a lineage specific response.

背景与目标： : 细胞水平的机械和3D空间线索对于在生长，修复或生物反应器中形成的新组织的组织和结构至关重要。成纤维细胞种子的3D胶原蛋白构建体已被用作生物人工细胞外基质 (ECM)，为嵌入的常驻细胞提供3D环境。当细胞附着在支架原纤维上时，它们会产生可量化的收缩力，这取决于细胞类型，细胞附着，细胞密度，生长因子和基质刚度。这项研究的目的是量化接种在硬度增加的构建体中的人真皮 (HDF) 和新生儿包皮成纤维细胞 (HNFF) 的细胞机械和分子反应。我们还测试了使用血清饥饿阻断早期附着对这些输出的影响。在凝胶收缩之前，将构建体置于0-10% 的单轴应变下以增加支架刚度，并使用张力培养力监测器 (t-cfm) 监测力的产生。在两种细胞类型中，增加的基质刚度在24小时内减少了可量化的细胞力 (高达70%) 的产生，并延迟了可测量的收缩的开始 (高达7倍)。可测量的力产生的延迟与细胞谱系有关，但与FCS无关。在刚度增加的构建体中，HDFs中MMP-2，TIMP-2和III型胶原表达的基因表达显着上调。HNFFs在这些基因表达中未显示任何显着变化，表明谱系特异性反应。

BACKGROUND & AIMS: :Skeletal muscle injury and regeneration are closely associated with an inflammatory reaction that is usually characterized by sequential recruitment of neutrophils and monocytes or macrophages. Selective macrophage depletion models have shown that macrophages are essential for complete regeneration of muscle fibers after freeze injuries, toxin injuries, ischemia-reperfusion, and hindlimb unloading and reloading. Although there is growing evidence that macrophages possess major myogenic capacities, it is not known whether the positive effects of macrophages can be optimized to stimulate muscle regrowth. We used in vivo and in vitro mouse models of atrophy to investigate the effects of stimulating macrophages with macrophage colony-stimulating factor (M-CSF) on muscle regrowth. When atrophied soleus muscles were injected intramuscularly with M-CSF, we observed a 1.6-fold increase in macrophage density and a faster recovery in muscle force (20%), combined with an increase in muscle fiber diameter (10%), after 7 days of reloading, compared with PBS-injected soleus muscles. Furthermore, coculture of atrophied myotubes with or without bone marrow-derived macrophages (BMDM) and/or M-CSF revealed that the combination of BMDMs and M-CSF was required to promote myotube growth (15%). More specifically, M-CSF promoted the anti-inflammatory macrophage phenotype, which in turn decreased protein degradation and MuRF-1 expression by 25% in growing myotubes. These results indicate that specific macrophage subsets can be stimulated to promote muscle cell regrowth after atrophy.

背景与目标： 骨骼肌损伤和再生与炎症反应密切相关，炎症反应通常以中性粒细胞和单核细胞或巨噬细胞的连续募集为特征。选择性巨噬细胞耗竭模型表明，巨噬细胞对于冷冻损伤，毒素损伤，缺血再灌注以及后肢卸载和重新加载后的肌纤维完全再生至关重要。尽管越来越多的证据表明巨噬细胞具有主要的肌源性能力，但尚不清楚是否可以优化巨噬细胞的积极作用以刺激肌肉再生。我们使用体内和体外萎缩小鼠模型来研究巨噬细胞集落刺激因子 (m-csf) 刺激巨噬细胞对肌肉再生的影响。当肌注m-csf肌注萎缩的比目鱼肌时，与注射PBS的比目鱼肌相比，在重装7天后，我们观察到巨噬细胞密度增加了1.6倍，肌力恢复更快 (20%)，并增加了肌纤维直径 (10%)。此外，具有或不具有骨髓来源的巨噬细胞 (BMDM) 和/或m-csf的萎缩肌管的共培养表明，需要BMDMs和m-csf的组合来促进肌管生长 (15%)。更具体地，m-csf促进抗炎巨噬细胞表型，这反过来通过25% 在生长的肌管中降低蛋白质降解和MuRF-1表达。这些结果表明，萎缩后可以刺激特定的巨噬细胞亚群以促进肌细胞再生。

BACKGROUND & AIMS: :Smooth muscle cells (SMC) make up the muscular portion of the gastrointestinal (GI) tract from the distal oesophagus to the internal anal sphincter. Coordinated contractions of these cells produce the motor patterns of GI motility. Considerable progress was made during the last 20 years to understand the basic mechanisms controlling excitation-contraction (E-C) coupling. The smooth muscle motor is now understood in great molecular detail, and much has been learned about the mechanisms that deliver and recover Ca2+ during contractions. The majority of Ca2+ that initiates contractions comes from the external solution and is supplied by voltage-dependent Ca2+ channels (VDCC). VDCC are regulated largely by the effects of K+ and non-selective cation conductances (NSCC) on cell membrane potential and excitability. Ca2+ entry is supplemented by release of Ca2+ from IP(3) receptor-operated stores and by mechanisms that alter the sensitivity of the contractile apparatus to changes in cytoplasmic Ca2+. Molecular studies of the regulation of smooth muscle have been complicated by the plasticity of SMC and difficulties in culturing these cells without dramatic phenotypic changes. Major questions remain to be resolved regarding the details of E-C coupling in human GI smooth muscles. New discoveries regarding molecular expression that give GI smooth muscle their unique properties, the phenotypic changes that occur in SMC in GI motor disorders, tissue engineering approaches to repair or replace defective muscular regions, and molecular manipulations of GI smooth muscles in animals models and in cell culture will be topics for exciting investigations in the future.

背景与目标： : 平滑肌细胞 (SMC) 构成胃肠道 (GI) 从远端食道到肛门内括约肌的肌肉部分。这些细胞的协调收缩产生胃肠道运动的运动模式。在过去的20年中，在了解控制激发-收缩 (E-C) 耦合的基本机制方面取得了相当大的进展。平滑肌运动现在已经在分子上得到了很大的了解，并且已经了解了在收缩过程中传递和恢复Ca2的机制。引发收缩的大部分Ca2来自外部解决方案，并由电压相关的Ca2通道 (VDCC) 提供。VDCC在很大程度上受K和非选择性阳离子电导 (NSCC) 对细胞膜电位和兴奋性的影响。通过从IP(3) 受体操作的存储中释放Ca2以及通过改变收缩装置对细胞质Ca2变化的敏感性的机制来补充Ca2的进入。平滑肌调节的分子研究因SMC的可塑性和难以培养这些细胞而没有显着的表型变化而变得复杂。关于人类胃肠道平滑肌中E-C耦合的细节，仍有主要问题有待解决。关于赋予GI平滑肌独特特性的分子表达的新发现，在GI运动障碍中SMC中发生的表型变化，修复或替换有缺陷的肌肉区域的组织工程方法，在动物模型和细胞培养中，GI平滑肌的分子操纵将成为未来令人兴奋的研究的主题。

BACKGROUND & AIMS: :We tested the hypothesis that brief static contraction of the triceps surae muscle causes reflex-induced increases in plasma arginine vasopressin (AVP) in anesthetized cats. Arterial blood samples, for measurement of plasma AVP, were taken before and after 30 s of electrically stimulated static contraction performed at a low intensity (<20% of maximal; n = 5), a high intensity (>70% of maximal; n = 7), and a high intensity after denervation of the triceps surae (n = 5). The low intensity contraction protocol was repeated during alpha-adrenergic blockade (n = 7) to minimize potential baroreflex-induced inhibition of AVP release. Passive stretch of the triceps surae was conducted (n = 5) to determine effects of muscle mechanoreceptor stimulation on the release of AVP. Low intensity contraction had no effect on plasma AVP. During alpha-adrenergic blockade, this same contraction intensity caused this peptide to increase from 12.8 +/- 2.1 to 17.7 +/- 2.6 pg/ml. High intensity contraction caused an increase in AVP (13.2 +/- 3.5 to 26.1 +/- 6.6 pg/ml) that was abolished by denervation (14.4 +/- 3. 7 vs. 17.1 +/- 6.6 pg/ml). Passive stretch had no effect on plasma AVP. These findings suggest that brief static contraction causes increases in plasma AVP that are reflex in nature, intensity dependent, opposed by the arterial baroreflex, and probably unrelated to muscle mechanoreceptor activation.

背景与目标： : 我们测试了以下假设: 肱三头肌的短暂静态收缩会导致麻醉猫的血浆精氨酸加压素 (AVP) 反射引起的增加。在低强度 (<最大20%; n = 5)，高强度 (> 最大70%; n = 7) 电刺激静态收缩30 s之前和之后采集用于测量血浆AVP的动脉血样本，以及肱三头肌去神经后的高强度 (n = 5)。在 α-肾上腺素能阻断 (n = 7) 期间重复低强度收缩方案，以最大程度地减少压力反射诱导的AVP释放的潜在抑制。进行肱三头肌的被动拉伸 (n = 5)，以确定肌肉机械感受器刺激对AVP释放的影响。低强度收缩对血浆AVP没有影响。在 α-肾上腺素能阻断期间，该相同的收缩强度导致该肽从12.8 +/- 2.1增加到17.7 +/- 2.6 pg/ml。高强度收缩引起AVP的增加 (13.2 +/- 3.5至26.1 +/- 6.6 pg/ml)，其被去神经支配消除 (14.4 +/-3.7对17.1 +/- 6.6 pg/ml)。被动拉伸对血浆AVP没有影响。这些发现表明，短暂的静态收缩会导致血浆AVP的增加，这种增加本质上是反射性的，强度依赖性的，与动脉压力反射相反，并且可能与肌肉机械感受器的激活无关。

BACKGROUND & AIMS: :The efficacy of selective endothelin (ET) receptor antagonists may be limited by a functional interaction between the ET(A) and ET(B) receptors. This interaction, also termed "cross talk", is characterized by the dependency of the inhibition of an ET-1 response due to antagonism of one ET receptor subtype upon concomitant antagonism of the other ET receptor subtype. Although a reduction in ET(A)-ET(B) receptor cross talk would presumably increase the efficacy of selective ET receptor antagonists, an approach that accomplishes this aim is largely absent due to a lack of mechanistic understanding. Toward this goal, we evaluated the characteristics and potential dependencies of cross talk in smooth muscle. Smooth muscle was adopted as an exemplar not only because cross talk is widely reported in this tissue type, thereby allowing numerous comparisons, but also significant controversy surrounds the use of selective versus nonselective ET receptor antagonists in ET-1-related pathophysiologies involving smooth muscle. Based on this evaluation, we suggest that ET(A)-ET(B) receptor cross talk is a dynamic process directed by either or both ET receptor subtypes and expressed to varying magnitudes depending on the ET-1 and selective ET receptor antagonist concentrations, tone due to intraluminal pressure/stretch, agonists acting at receptors other than the ET(A)/ET(B) receptors, and endothelial/epithelial function. It is speculated that ET(A)-ET(B) receptor cross talk occurs through signal transduction pathways along with changes at the receptor level. Pharmacologic intervention of the signaling pathways could increase the therapeutic efficacy of ET receptor antagonists.

背景与目标： : 选择性内皮素 (ET) 受体拮抗剂的功效可能受到ET (a) 和ET(B) 受体之间功能相互作用的限制。这种相互作用，也称为 “串扰”，其特征在于由于一种ET受体亚型的拮抗作用而引起的ET-1反应的抑制对另一种ET受体亚型的伴随拮抗作用的依赖性。尽管ET (a)-ET(B) 受体串扰的减少可能会增加选择性ET受体拮抗剂的功效，但由于缺乏机理理解，基本上没有实现这一目标的方法。为此，我们评估了平滑肌中串扰的特征和潜在依赖性。平滑肌被用作示例，不仅因为在这种组织类型中广泛报道了串扰，从而允许进行大量比较，而且在涉及平滑肌的ET-1-related病理生理中使用选择性与非选择性ET受体拮抗剂也存在重大争议。基于此评估，我们建议ET(A)-ET(B) 受体串扰是由ET受体亚型之一或两者指导的动态过程，并根据ET-1和选择性ET受体拮抗剂的浓度表达为不同的幅度，由于腔内压力/拉伸，作用于ET(A)/ET(B) 受体以外的受体和内皮/上皮功能的激动剂。据推测，ET(A)-ET(B) 受体串扰是通过信号转导途径以及受体水平的变化而发生的。信号通路的药物干预可以提高ET受体拮抗剂的治疗效果。

BACKGROUND & AIMS: :This study compared the effects of fatigue on corticospinal responsiveness in the upper- and lower-limb muscles of the same participants. Seven healthy males performed a 2-min maximal voluntary isometric contraction of the elbow flexors or knee extensors on four separate days. Electromyographic responses were elicited by nerve stimulation (maximal M-wave) in all sessions and by transcranial magnetic stimulation (motor-evoked potential; silent period) and spinal tract stimulation (cervicomedullary or thoracic motor-evoked potentials; silent period) in one session each per limb. During sustained maximal voluntary contractions, motor-evoked potential area normalised to M-waves increased from baseline in biceps brachii (155 ± 55%) and rectus femoris (151 ± 44%) (both p ≤ 0.045). At the end of maximal voluntary contractions, spinal tract motor-evoked potential area normalised to M-waves was smaller than baseline in biceps brachii (74 ± 23%; p = 0.012) but not rectus femoris (108 ± 40%; p = 0.999). The ratio of motor-evoked potential to spinal tract-evoked potential areas increased dramatically from 90 to 115 s in biceps brachii (p = 0.001) but not in rectus femoris (p = 0.999). Silent period durations increased similarly in both muscles (p ≤ 0.008) after transcranial and spinal stimulation. Sustained maximal contractions elicit different neurophysiological adjustments in upper- and lower-limb muscles. Specifically, motoneuronal excitability was reduced in biceps brachii, but not in rectus femoris, and this reduction required greater compensatory adjustments from the motor cortex. Therefore, changes in cortical and spinal excitability during sustained maximal exercise are likely specific to the muscle performing the task.

背景与目标： : 这项研究比较乏力对同一参与者上肢和下肢肌肉皮质脊髓反应性的影响。七名健康男性在四个不同的日子里对肘部屈肌或膝伸肌进行了2分钟的最大自愿等距收缩。在所有会话中通过神经刺激 (最大M波) 以及经颅磁刺激 (运动诱发电位; 静默期) 和脊髓道刺激 (颈髓或胸腔运动诱发电位; 静默期) 引起肌电图反应每个肢体。在持续最大自愿收缩期间，肱二头肌 (155   ±   55%) 和股直肌 (151   ±   44%) (均p  ≤   0.045) 的运动诱发电位区域从基线增加到M波。在最大自愿性收缩结束时，肱二头肌 (74   ±   23%; P   =   0.012) 的脊髓道运动诱发电位面积标准化为M波，小于基线，而股直肌 (108   ±   40%; P   =   0.999)。肱二头肌 (p   =   0.001) 的运动诱发电位与脊髓束诱发电位区域的比率从90到115  s急剧增加，而股直肌 (p   =   0.999) 则没有。经颅和脊柱刺激后，两种肌肉的静默期持续时间相似地增加 (p  ≤   0.008)。持续的最大收缩会引起上肢和下肢肌肉的不同神经生理调节。具体来说，肱二头肌的运动神经元兴奋性降低，但股直肌却没有，这种降低需要运动皮层进行更大的补偿性调整。因此，持续最大运动期间皮质和脊柱兴奋性的变化可能是特定于执行任务的肌肉的。

BACKGROUND & AIMS: :Radix astragali is a popular traditional herbal medicine that provides significant protection against tissue injury in various models of oxidative stress-related diseases. In this study, we aimed to investigate whether administration of Radix astragali prevented atrophy in both slow- and fast-twitch muscles following cast immobilization. Twenty-seven 12-week-old male F344 rats were divided into three experimental groups: control (CON), immobilized (IM), and immobilized with Radix astragali administration (IM+AR). Rats in the IM and IM+AR groups were subjected to immobilization of both lower extremities using casting-tape for 14 days. Rats in the IM+AR group were orally administered a decoction of Radix astragali daily for 21 days beginning 7 days before cast immobilization. As expected, rats in the IM group showed significant decreases (P < 0.05) in soleus and plantaris muscle-to-body weight ratios by 74.3% and 70.5%, respectively, compared with those in the CON group. Administration of Radix astragali significantly reversed (+35.5%) the weight reduction observed in soleus muscle, but not in the plantaris muscle, compared with that in the IM group. Furthermore, administration of Radix astragali inhibited MuRF1 mRNA expression only in the soleus muscle during cast immobilization. Our results demonstrated that administration of Radix astragali suppressed the immobilization-induced reductions in skeletal muscle mass and expression of MuRF1 mRNA in slow-twitch soleus muscles, but not in fast-twitch plantaris muscles.

背景与目标： : 黄芪是一种流行的传统草药，在各种氧化应激相关疾病模型中提供对组织损伤的显着保护。在这项研究中，我们旨在研究黄芪的给药是否可以预防石膏固定后缓慢和快速抽搐肌肉的萎缩。将27只12周龄雄性F344大鼠分为三个实验组: 对照组 (CON)，固定化 (IM) 和固定化黄芪给药 (IM AR)。IM和IM AR组的大鼠使用流延胶带固定两个下肢14天。IM AR组的大鼠在石膏固定前7天开始每天口服黄芪汤21天。正如预期的那样，与CON组相比，IM组大鼠比目鱼肌和plantaris的肌肉重量比分别显着降低了74.3% 和70.5% (P <0.05)。与IM组相比，黄芪的给药显着逆转 (35.5%) 比目鱼肌中观察到的重量减少，但在plant肌中没有。此外，黄芪的给药仅在石膏固定期间抑制比目鱼肌中的MuRF1 mRNA表达。我们的结果表明，黄芪的给药抑制了固定诱导的慢抽搐比目鱼肌骨骼肌质量的减少和MuRF1 mRNA的表达，但抑制了快抽搐的plant肌。

BACKGROUND & AIMS: :1. The influence of perinatal and pubertal gonadal androgens on acetylcholinesterase (AChE) activity was studied in the hormone-sensitive levator ani (LA) and extensor digitorum longus (EDL) muscles of adult male rats (105 days). 2. The hormone was withdrawn by gonadectomy at various ages and the effects on AChE and weight were compared with those induced by chronic denervation of both muscles from adult rats. 3. Gonadectomy of infantile (2-30 days) rats prevented LA muscle growth, and reduced total AChE activity to values similar to those found in denervated muscles (15% of control). The EDL muscles were slightly affected and only in rats castrated on the 2nd postnatal day. 4. When the rats were castrated at puberty (45 days), LA muscle weight and total AChE activity were reduced to 20% and 18% of control values, respectively. 5. Gonadectomy of adult (60 and 75 days) rats led to atrophy of the LA muscle (to 29% of control) and reduced the total AChE activity (to 40% of control). 6. AChE activity per unit weight was reduced by 30% in rats castrated from 5 to 20 days of age, and increased by 30% in both LA and EDL muscles from rats castrated in adulthood. Gonadectomy before puberty prevented total AChE in the LA from increasing above the levels detected in chronically denervated muscles. 7. Gonadectomy after puberty reduced total AChE of the LA but never to the extent caused by muscle denervation. 8. It is concluded that testosterone regulates AChE in the LA by early priming of the motoneuron and by pubertal stimulation of enzyme synthesis, the synthesis being dependent on intact innervation.

背景与目标： : 1。在成年雄性大鼠 (105天) 的激素敏感性提ani (LA) 和趾长伸肌 (EDL) 肌肉中研究了围产期和青春期性腺雄激素对乙酰胆碱酯酶 (AChE) 活性的影响。2.在不同年龄的性腺切除术中停用激素，并将其对疼痛和体重的影响与成年大鼠两种肌肉慢性去神经支配引起的影响进行比较。3.婴儿 (2-30天) 大鼠的性腺切除术可防止LA肌肉生长，并将总AChE活性降低至与失神经肌肉相似的值 (对照15%)。EDL肌肉受到轻微影响，仅在出生后第二天cast割的大鼠中。4.当大鼠在青春期 (45天) 去势时，LA肌肉重量和总AChE活性分别降低至对照值的20% 和18%。5.成年 (60和75天) 大鼠的性腺切除术导致LA肌肉萎缩 (至对照29%) 并降低总AChE活性 (至对照40%)。6.在5至20日龄的大鼠中，每单位重量的AChE活性因30% 而降低，而在成年后被阉割的大鼠的LA和EDL肌肉中，每单位重量的AChE活性因30% 而增加。青春期前的性腺切除术可防止LA的总疼痛增加到慢性失神经肌肉中检测到的水平以上。7.青春期后的性腺切除术减少了LA的总疼痛，但从未达到由肌肉神经支配引起的程度。8.结论是，睾丸激素通过运动神经元的早期启动和青春期刺激酶合成来调节LA中的AChE，该合成取决于完整的神经支配。

BACKGROUND & AIMS: :Na/Ca exchange is the dominant calcium (Ca) efflux mechanism in cardiac myocytes. Although our knowledge of exchanger function (NCX1 in the heart) was originally established using biochemical and electrophysiological tools such as cardiac sarcolemmal vesicles and the giant patch technique [1-4], many advances in our understanding of the physiological/pathophysiological roles of NCX1 in the heart have been obtained using a suite of genetically modified mice. Early mouse studies focused on modification of expression levels of NCX1 in the ventricles, with transgenic overexpressors, global NCX1 knockout (KO) mice (which were embryonic lethal if homozygous), and finally ventricular-specific NCX1 KO [5-12]. We found, to our surprise, that ventricular cardiomyocytes lacking NCX1 can survive and function by engaging a clever set of adaptations to minimize Ca entry, while maintaining contractile function through an increase in excitation-contraction (EC) coupling gain [5,6,13]. Having studied ventricular NCX1 ablation in detail, we more recently focused on elucidating the role of NCX1 in the atria through altering NCX1 expression. Using a novel atrial-specific NCX1 KO mouse, we found unexpected changes in atrial cell morphology and calcium handling, together with dramatic alterations in the function of sinoatrial node (SAN) pacemaker activity. In this review, we will discuss these findings and their implications for cardiac disease.

背景与目标： : Na/Ca交换是心肌细胞中主要的钙 (Ca) 流出机制。尽管我们对交换器功能 (心脏NCX1) 的了解最初是使用生化和电生理工具 (例如心脏肌膜囊泡和巨型贴片技术) 建立的 [1-4]，使用一组转基因小鼠，我们对NCX1在心脏中的生理/病理生理作用的理解取得了许多进展。早期的小鼠研究集中在脑室中NCX1的表达水平的修饰，转基因过表达，全球NCX1基因敲除 (KO) 小鼠 (如果纯合子是胚胎致死性的)，最后是心室特异性NCX1 KO [5-12]。令我们惊讶的是，我们发现缺乏NCX1的心室心肌细胞可以通过参与一组巧妙的适应来最小化Ca的进入而存活和发挥功能，同时通过增加兴奋-收缩 (EC) 耦合增益来维持收缩功能 [5,6，13]。在详细研究了心室NCX1消融之后，我们最近着重于通过改变NCX1表达来阐明NCX1在心房中的作用。使用新型的心房特异性NCX1 KO小鼠，我们发现心房细胞形态和钙处理的意外变化，以及窦房结 (SAN) 起搏器活动功能的显着变化。在这篇综述中，我们将讨论这些发现及其对心脏病的影响。

BACKGROUND & AIMS: :Repeated stimulation of unfatigued rodent fast-twitch skeletal muscle accelerates the kinetics of tension relaxation through an unknown mechanism. This effect varies with muscle type and stimulation parameters, and has been observed at physiological temperatures for submaximal but not maximal contractions. The purpose of this study was to compare relaxation kinetics of C57BL/6 mouse lumbrical muscles ex vivo from maximal isometric force (500 Hz for 20 ms) when evoked before (pre) and after (post) an intervening tetanic contraction at 37°C. During post contractions, we noted significant increases in the rate of tension decline during both the slow linear phase and the fast exponential phase of relaxation, as well as a reduced duration of the slow phase of relaxation compared with pre contractions (all P<0.05). This is the first demonstration of enhanced slow and fast relaxation phases from maximal isometric tension induced by prior stimulation in intact muscle at a physiological temperature.

背景与目标： : 反复刺激未疲劳的啮齿动物快速抽搐骨骼肌通过未知机制加速张力松弛的动力学。这种效果随肌肉类型和刺激参数而变化，并且在生理温度下观察到亚最大收缩而不是最大收缩。这项研究的目的是比较C57BL/6小鼠腰肌在体外的最大等轴测力 (500 hz，持续20  ms) 的松弛动力学，当在37 °C的介入强直收缩之前 (前) 和之后 (后) 诱发时。在收缩后期间，我们注意到在松弛的缓慢线性阶段和快速指数阶段期间，张力下降的速率显着增加，并且与收缩前相比，松弛的缓慢阶段的持续时间减少 (所有P<0.05)。这是在生理温度下由完整肌肉的先前刺激引起的最大等距张力增强的慢速和快速松弛阶段的首次证明。

BACKGROUND & AIMS: :The cell adhesion molecule N-CAM is localized to the adult neuromuscular junction but is also expressed in the extrajunctional membrane of denervated muscles concurrent with extrajunctional acetylcholine receptors. Here we used N-CAM immunohistochemistry to determine whether we could detect early denervation in hindlimb muscles of the G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS). In denervated wild type mouse muscles, N-CAM immunoreactivity on the sarcolemma of all fiber types and within the sarcoplasm of only type IIA fibers was detected at day 2: approximately 30% of the muscle fibers in cross-section were fully circumscribed by N-CAM immunoreactivity and approximately 25% of fibers were incompletely circumscribed. The proportion of the latter fibers remained constant over the next 8 days as the proportions of the former fibers increased exponentially. Thereafter, fully circumscribed muscle fibers increased to a maximum by 30 days with a concomitant fall in the incompletely circumscribed fibers. Hence, early muscle denervation was detected by the incomplete circumscription of fiber membranes by N-CAM immunoreactivity with full circumscription and intracellular localization indicating more long-term denervation. In the G93A transgenic mouse, rapid denervation of fast-twitch muscles was readily detected by a corresponding proportion of muscle fibers in cross-section with positive N-CAM immunoreactivity. The proportions of incompletely and completely circumscribed muscle fibers corresponded well with the rate of decline in intact motor units and reduced muscle contractile forces. Progressively more fully circumscribed muscle fibers became evident with age. We conclude that the N-CAM immunoreactivity on muscle fiber membranes in muscle cross-sections provides a sensitive means of detecting early muscle fiber denervation.

背景与目标： : 细胞粘附分子N-CAM定位于成人神经肌肉接头，但也与接头外乙酰胆碱受体同时在失神经支配肌肉的结外膜中表达。在这里，我们使用N-CAM免疫组织化学来确定是否可以检测到肌萎缩性侧索硬化症 (ALS) G93A转基因小鼠模型后肢肌肉的早期去神经支配。在失神经的野生型小鼠肌肉中，在第2天检测到对所有纤维类型的肌膜和仅IIA型纤维的肌浆内的N-CAM免疫反应性: 横截面中大约30% 的肌肉纤维被N-CAM免疫反应性完全限制，并且大约25% 的纤维不完全限制。后一种纤维的比例在接下来的8天内保持恒定，因为前一种纤维的比例呈指数增长。此后，完全外接的肌肉纤维增加到最大30天，同时不完全外接的纤维也随之下降。因此，通过N-CAM免疫反应性通过纤维膜的不完全外接检测到早期肌肉去神经，并具有完全外接和细胞内定位，表明更长期的去神经。在G93A转基因小鼠中，通过具有正N-CAM免疫反应性的横截面中相应比例的肌纤维很容易检测到快速抽动肌肉的快速去神经。不完全和完全外接的肌肉纤维的比例与完整运动单位的下降速度和肌肉收缩力的降低非常吻合。随着年龄的增长，逐渐变得更加完全限制的肌肉纤维。我们得出的结论是，肌肉横截面中肌纤维膜上的N-CAM免疫反应性提供了检测早期肌纤维去神经支配的敏感手段。

BACKGROUND & AIMS: :Paraspinal muscle fatigability during various trunk extension tests has been widely investigated by electromyography (EMG), and its task-dependency is established recently. Hip extensor muscle fatigability during the Sorensen test has been reported. The aim of the present experiments was to evaluate the task-dependency of back and hip extensor muscle fatigue during two variants of the Sorensen test. We hypothesized that the rate of muscular fatigue of the hip and back extensor muscles varies according to the test position. Twenty healthy young males with no history of low back pain volunteered to participate in this cross-sectional study. They were asked to perform two body weight-dependent isometric back extension tests (S1 = Sorensen test; S2 = modified Sorensen on a 45 degrees Roman chair). Surface EMG activity of the paraspinal muscles (T10 and L5 levels) and hip extensor muscles (gluteus maximus; biceps femoris) was recorded, and muscular fatigue was assessed through power spectral analysis of the EMG data by calculating the rate of median power frequency change. We observed hip extensor muscle fatigue simultaneously with paraspinal muscle fatigue during both Sorensen variants. However, only L5 level EMG fatigue indices showed a task-dependency effect between S1 and S2. Hip extensor muscles appear to contribute to load sharing of the upper body mass during both Sorensen variants, but to a different extent because L5 level fatigue differs between the Sorensen variants. Our findings suggest that task-dependency has to be considered when EMG variables are compared between two types of lumbar muscle-fatiguing tasks.

背景与目标： : 肌电图 (EMG) 已广泛研究了各种躯干伸展测试过程中的脊柱旁肌肉疲劳能力，并且最近建立了其任务依赖性。已经报道了Sorensen测试期间的髋伸肌易疲劳性。本实验的目的是评估Sorensen测试的两个变体中背部和髋部伸肌乏力的任务依赖性。我们假设髋部和背部伸肌的肌肉乏力率根据测试位置而变化。20名没有腰痛病史的健康年轻男性自愿参加了这项横断面研究。他们被要求进行两次体重相关的等距背部伸展测试 (S1 = Sorensen测试; S2 = 在45度罗马椅上修改后的Sorensen)。记录椎旁肌 (T10和L5水平) 和髋伸肌 (臀大肌; 股二头肌) 的表面EMG活动，并通过计算中值功率频率变化率，通过EMG数据的功率谱分析评估肌肉乏力。在两个Sorensen变体中，我们同时观察到了髋关节伸肌乏力和椎旁肌乏力。但是，只有L5级EMG乏力指数在S1和s2之间显示出任务依赖性效应。在两个Sorensen变体中，髋关节伸肌似乎都有助于上半身质量的负荷分担，但程度不同，因为Sorensen变体之间的L5水平乏力有所不同。我们的发现表明，在比较两种类型的腰肌疲劳任务之间的EMG变量时，必须考虑任务依赖性。