Control of cardiac contraction by sodium: Promises,reckonings, and new beginnings

Several generations of cardiac physiologists have verified that basal cardiac contractility depends strongly on the transsarcolemmal Na gradient, and the underlying molecular mechanisms that link cardiac excitation-contraction coupling (ECC) to the Na gradient have been elucidated in good detail for more than 30 years. In brief, small increases of cytoplasmic Na push cardiac (NCX1) Na/Ca exchangers to increase contractility by increasing the myocyte Ca load. Accordingly, basal cardiac contractility is expected to be physiologically regulated by pathways that modify the cardiac Na gradient and the function of Na transporters. Assuming that this expectation is correct, it remains to be elucidated how in detail signaling pathways affecting the cardiac Na gradient are controlled in response to changing cardiac output requirements. Some puzzle pieces that may facilitate progress are outlined in this short review. Key open issues include (1) whether the concept of local Na gradients is viable, (2) how in detail Na channels, Na transporters and Na/K pumps are regulated by lipids and metabolic processes, (3) the physiological roles of Na/K pump inactivation, and (4) the possibility that key diffusible signaling molecules remain to be discovered.     

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 high- frequency 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 Iongus （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.     

MVIC运动不能提高大学生篮球运动员的激活后增强效应

本研究旨在探讨激活后增强效应(post-activation potentiation, PAP)对大学生篮球运动员上肢力量表现和肌肉损伤指标的影响,以及不同最大自主等长收缩(maximal voluntary isometric contraction, MVIC)时间诱发激活后增强效应后,对卧推(bench press throw, BPT)表现的影响。本研究招募30名大学生男性篮球运动员进行重复交叉实验。所有受试者均接受3组3 s卧推MVICs (3 MVICs)、3组5 s卧推MVICs (5 MVICs)、对照控制(CON)共3次干预,记录推掷高度与杠铃腾空时间,并分析推掷高度、力量与功率的峰值。研究表明:3 MVICs、5 MVICs、CON处理后,卧推高度在后测各时间点皆显著低于前测平均值,功率峰值在第4分钟、第8分钟及后测平均值上,皆显著低于前测平均值。但是,力量峰值在后测各时间点与前测平均值均无显著性差异。本研究初步认为给予较长的组间恢复时间,3 MVICs、5 MVICs产生肌肉疲劳的程度可能高于诱发PAP的程度,进而无法提升训练良好运动员的上肢爆发力表现。     

Passiflora plastome sequencing reveals widespread genomic rearrangements

Although past studies have included Passiflora among angiosperm lineages with highly rearranged plastid genomes (plastomes), knowledge about plastome organization in the genus is limited. So far only one draft and one complete plastome have been published. Expanded sampling of Passiflora plastomes is needed to understand the extent of the genomic rearrangement in the genus, which is also unusual in having biparental plastid inheritance and plastome‐genome incompatibility. We sequenced 15 Passiflora plastomes using either Illumina paired‐end or shotgun cloning and Sanger sequencing approaches. Assembled plastomes were annotated using Dual Organellar GenoMe Annotator (DOGMA) and tRNAscan‐SE. The Populus trichocarpa plastome was used as a reference to estimate genomic rearrangements in Passiflora by performing whole genome alignment in progressiveMauve. The phylogenetic distribution of rearrangements was plotted on the maximum likelihood tree generated from 64 plastid encoded protein genes. Inverted repeat (IR) expansion/contraction and loss of the two largest hypothetical open reading frames, ycf1 and ycf2, account for most plastome size variation, which ranges from 139 262 base pairs (bp) in P. biflora to 161 494 bp in P. pittieri. Passiflora plastomes have experienced numerous inversions, gene and intron losses along with multiple independent IR expansions and contractions resulting in a distinct organization in each of the three subgenera examined. Each Passiflora subgenus has a unique plastome structure in terms of gene content, order and size. The phylogenetic distribution of rearrangements shows that Passiflora has experienced widespread genomic changes, suggesting that such events may not be reliable phylogenetic markers.     

Realized niche shift associated with Galinsoga quadriradiata (Asteraceae) invasion in China

粗毛牛膝菊在中国的入侵与生态位漂移有关 在外来物种入侵和扩散过程中,生态位的漂移可能起到了重要作用。粗毛牛膝菊(Galinsoga quadriradiata) 在中国已造成了较为严重的入侵,占据了许多与其原产地不同的气候区。为此,本研究力图揭示粗毛牛膝菊入侵过程中的气候生态位漂移,分析其在该物种入 侵中国过程中可能发挥的作用。本研究结合粗毛牛膝菊原 产地和入侵地的分布点与气候数据, 采用Maxent模型预测了其在中国潜在的分布,并采用主成分分析的方法评估 了在入侵中国过程中粗毛牛膝菊气候生态位的漂移。模型结果显示,该物种原产地种群和入侵地种群之间只 有32.7%的生态位重叠,两个种群的生态位相似性较低(Schoener's D = 0.093, P < 0.005),这暗示了在其入侵过程中发生了生态位漂移。相比于其原产地种群,其在中国的入侵种群气候生态位的整体范围和中心都明 显地漂移向了温度更低、降水更少的区域;中国南方大部分区域属于粗毛牛膝菊的稳定适生区,而位于入侵 前沿的北方地区则存在局域适应和潜在拓殖区域。这些研究结果说明,粗毛牛膝菊在中国的入侵种群仍处于准平衡阶段,未来有可能继续向新的适生区扩散入侵,其生态位的变化有力地解释了为什么该物种在中国的入侵性强、危害范围大。     

Somatostatin induces rapid contraction of neuroendocrine cells

The peptide hormone somatostatin, as well as the somatostatin analog octreotide, induces rapid morphological changes in neuroendocrine cells. The effect can be detected in less than 2 min: retraction fibers are formed, cells round up and cell-cell contacts are broken. Somatostatin-dependent cell contraction is inhibited by Y-27632, indicating that this effect is dependent on Rho kinase. In BON1 cells, the somatostatin-induced inhibition of forskolin-induced secretion of chromogranin A is not blocked by Y-27632. It is therefore concluded that the inhibitory effect of somatostatin in forskolin-stimulated cells is not dependent on cell contraction.     

Age-related fatigability in knee extensors and knee flexors during dynamic fatiguing contractions

This study investigated the effects of dynamic knee extension and flexion fatiguing task on torque and neuromuscular responses in young and older individuals. Eighteen young (8 males; 25.1 ± 3.2 years) and 17 older (8 males; 69.7 ± 3.7 years) volunteered. Following a maximal voluntary isometric contraction test, participants performed a fatiguing task involving 22 maximal isokinetic (concentric) knee extension and flexion contractions at 60°/s, while surface EMG was recorded simultaneously from the knee extensors (KE) and flexors (KF). Fatigue-induced relative torque reductions were similar between age groups for KE (peak torque decrease: 25.15% vs 26.81%); however, KF torque was less affected in older individuals (young vs older peak torque decrease: 27.6% vs 11.5%; p < 0.001) and this was associated with greater increase in hamstring EMG amplitude (p < 0.001) and hamstrings/quadriceps peak torque ratio (p < 0.01). Furthermore, KE was more fatigable than KF only among older individuals (peak torque decrease: 26.8% vs 11.5%; p < 0.001). These findings showed that the age-related fatigue induced by a dynamic task was greater for the KE, with greater age-related decline in KE compared to KF.     

Development of a novel MATLAB-based framework for implementing mechanical joint stability constraints within OpenSim musculoskeletal models

The Static Optimization (SO) solver in OpenSim estimates muscle activations and forces that only equilibrate applied moments. In this study, SO was enhanced through an open-access MATLAB interface, where calculated muscle activations can additionally satisfy crucial mechanical stability requirements. This Stability-Constrained SO (SCSO) is applicable to many OpenSim models and can potentially produce more biofidelic results than SO alone, especially when antagonistic muscle co-contraction is required to stabilize body joints. This hypothesis was tested using existing models and experimental data in the literature. Muscle activations were calculated by SO and SCSO for a spine model during two series of static trials (i.e. simulation 1 and 2), and also for a lower limb model (supplementary material 2). In simulation 1, symmetric and asymmetric flexion postures were compared, while in simulation 2, various external load heights were compared, where increases in load height did not change the external lumbar flexion moment, but necessitated higher EMG activations. During the tasks in simulation 1, the predicted muscle activations by SCSO demonstrated less average deviation from the EMG data (6.8% −7.5%) compared to those from SO (10.2%). In simulation 2, SO predicts constant muscle activations and forces, while SCSO predicts increases in the average activations of back and abdominal muscles that better match experimental data. Although the SCSO results are sensitive to some parameters (e.g. musculotendon stiffness), when considering the strategy of the central nervous system in distributing muscle forces and in activating antagonistic muscles, the assigned activations by SCSO are more biofidelic than SO.     

Mechanical analysis of intestinal contractility in a neonatal maternal deprivation irritable bowel syndrome rat model

The aims of the present study are to investigate biomechanical properties and provide mechanical analysis of contractility in ileum and colon in a neonatal maternal deprivation (NMD) irritable bowel syndrome (IBS) rat model. Mechanical testing was done on segments from ileum and colon in 25 IBS rats and 13 Control rats. Morphometric data were obtained from digitized images of the segments at no-load and zero-stress states. Pressure and diameter changes were measured during flow and ramp distensions under active and passive experimental conditions. Circumferential stresses (force per area) and strains (deformation) were computed with referenced to the zero-stress state. The contraction frequency was analyzed. Contraction thresholds and maximum contraction amplitude were calculated in terms of mechanical stress and strain. Compared with controls, the IBS rats had lower body weight (P < 0.01), smaller colonic opening angle (P < 0.05), higher colonic contraction frequency (P < 0.05 and P < 0.01) and lower contraction thresholds of pressure, stress and strain in both ileum and colon (P < 0.05 and P < 0.01). The maximum contraction pressure, stress and strain did not differ between IBS and Control groups (P > 0.05). In conclusion, the pressure, stress, and strain to evoke contractility in ileum and colon were lower whereas the frequency of induced colon contractions was higher in NMD IBS rats compared to normal rats. Furthermore, zero-stress state remodeling occur in colon in NMD IBS rats. Further studies on the association between intestinal biomechanical properties, hypersensitivity and afferent signaling in the IBS animal models are warranted.