Pattern Of Contractile Activity Research Articles

Heart mechanical and hemodynamic parameters of a beetle, Tenebrio molitor, at selected ages.

The physiological processes that occur during the aging of insects are poorly understood. The aim of this study was to describe the changes in contractile activity and hemodynamic parameters of the heart that take place as the coleopteran beetle, Tenebrio molitor, ages. The frequency of heart contractions in beetles that had just undergone metamorphosis (median 24.7 beats/min) was significantly lower than the frequency of heart contractions in older beetles. In 56% of beetles that were<1week of age, a pattern of contractile activity with alternating periods of higher and lower contraction frequency was detected, suggesting that some posteclosion developmental processes occur during the first week of adulthood. All beetles that were 1week of age showed a regular rhythm of heart contractions (median 72 beats/min). In older beetles, abnormalities such as heart arrhythmias or heart arrest were observed. The incidence of arrhythmia as well as the arrhythmicity index was highest in beetles that were 8-18weeks old. The calculated stroke volume (SV) was also found to increase from eclosion to 12weeks of age, and then decreased as adults aged further. Interestingly, cardiac output increased gradually, but the ejection fraction did not change significantly with age.

The role of skeletal muscle contractile duration throughout the whole day: reducing sedentary time and promoting universal physical activity in all people.

A shared goal of many researchers has been to discover how to improve health and prevent disease, through safely replacing a large amount of daily sedentary time with physical activity in everyone, regardless of age and current health status. This involves contrasting how different muscle contractile activity patterns regulate the underlying molecular and physiological responses impacting health‐related processes. It also requires an equal attention to behavioural feasibility studies in extremely unfit and sedentary people. A sound scientific principle is that the body is constantly sensing and responding to changes in skeletal muscle metabolism induced by contractile activity. Because of that, the rapid time course of health‐related responses to physical inactivity/activity patterns are caused in large part directly because of the variable amounts of muscle inactivity/activity throughout the day. However, traditional modes and doses of exercise fall far short of replacing most of the sedentary time in the modern lifestyle, because both the weekly frequency and the weekly duration of exercise time are an order of magnitude less than those for people sitting inactive. This can explain why high amounts of sedentary time produce distinct metabolic and cardiovascular responses through inactivity physiology that are not sufficiently prevented by low doses of exercise. For these reasons, we hypothesize that maintaining a high metabolic rate over the majority of the day, through safe and sustainable types of muscular activity, will be the optimal way to create a healthy active lifestyle over the whole lifespan.

Unravelling the mechanisms regulating muscle mitochondrial biogenesis.

Skeletal muscle is a tissue with a low mitochondrial content under basal conditions, but it is responsive to acute increases in contractile activity patterns (i.e. exercise) which initiate the signalling of a compensatory response, leading to the biogenesis of mitochondria and improved organelle function. Exercise also promotes the degradation of poorly functioning mitochondria (i.e. mitophagy), thereby accelerating mitochondrial turnover, and preserving a pool of healthy organelles. In contrast, muscle disuse, as well as the aging process, are associated with reduced mitochondrial quality and quantity in muscle. This has strong negative implications for whole-body metabolic health and the preservation of muscle mass. A number of traditional, as well as novel regulatory pathways exist in muscle that control both biogenesis and mitophagy. Interestingly, although the ablation of single regulatory transcription factors within these pathways often leads to a reduction in the basal mitochondrial content of muscle, this can invariably be overcome with exercise, signifying that exercise activates a multitude of pathways which can respond to restore mitochondrial health. This knowledge, along with growing realization that pharmacological agents can also promote mitochondrial health independently of exercise, leads to an optimistic outlook in which the maintenance of mitochondrial and whole-body metabolic health can be achieved by taking advantage of the broad benefits of exercise, along with the potential specificity of drug action.

Regulation of gastrointestinal motility—insights from smooth muscle biology

Gastrointestinal motility results from coordinated contractions of the tunica muscularis, the muscular layers of the alimentary canal. Throughout most of the gastrointestinal tract, smooth muscles are organized into two layers of circularly or longitudinally oriented muscle bundles. Smooth muscle cells form electrical and mechanical junctions between cells that facilitate coordination of contractions. Excitation-contraction coupling occurs by Ca(2+) entry via ion channels in the plasma membrane, leading to a rise in intracellular Ca(2+). Ca(2+) binding to calmodulin activates myosin light chain kinase; subsequent phosphorylation of myosin initiates cross-bridge cycling. Myosin phosphatase dephosphorylates myosin to relax muscles, and a process known as Ca(2+) sensitization regulates the activity of the phosphatase. Gastrointestinal smooth muscles are 'autonomous' and generate spontaneous electrical activity (slow waves) that does not depend upon input from nerves. Intrinsic pacemaker activity comes from interstitial cells of Cajal, which are electrically coupled to smooth muscle cells. Patterns of contractile activity in gastrointestinal muscles are determined by inputs from enteric motor neurons that innervate smooth muscle cells and interstitial cells. Here we provide an overview of the cells and mechanisms that generate smooth muscle contractile behaviour and gastrointestinal motility.

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Calcium-dependent gene regulation in myocyte hypertrophy and remodeling.

Striated myocytes from skeletal and cardiac muscle tissues are excitable cells that utilize calcium to trigger actomyosin cross-bridge formation in the generation ofcontractile force. Myocytes respond to different temporalpatterns of activation and changing workloads by alteringprograms of gene expression that adjust cellular mass, kinetic properties of contractile proteins, and metabolic capacity to match muscle phenotypes to different physiological demands. In disease states, modulation of geneexpression in myocytes as a function of contractile workload may have maladaptive consequences. We have considered the general hypothesis that changes in intracellular calcium resulting from different patterns of contractileactivity not only serve to drive muscle contractions, butalso provide a primary stimulus to activity-dependentchanges in gene expression and muscle phenotype. Accordingly, we have investigated the role of calcium-regulated signaling molecules in controlling transcription ofgenes that are subject to activity-dependent regulation.Using cultured myocytes and transgenic mouse models,we have defined features of signaling cascades that modulate transcription of specific contractile protein isoforms, mitochondrial biogenesis, and myocyte mass.These pathways involve calmodulin-dependent proteinkinases, the calcium-calmodulin-regulated protein phosphatase calcineurin, transcription factors of the MEF-2,NF-AT, and PGC-1 families, and proteins of the MCIP(DSCR1) gene family. Calcium released from discrete intracellular and extracellular pools exerts different effectson the kinetics of activation of specific transcription factors in striated myocytes. These results are reviewed andpresented in the context of a conceptual model for activity-dependent gene regulation in myocytes...

Regulatory Elements Governing Transcription in Specialized Myofiber Subtypes

Skeletal myofibers of vertebrates acquire specialized metabolic and physiological properties as a consequence of developmental cues in the embryo and different patterns of contractile activity in the adult. The myoglobin gene is regulated stringently in muscle fibers, such that high myoglobin expression is observed in mitochondria-rich, oxidative myofibers (Types I and IIa) compared with glycolytic fibers (Type IIb). Using germ-line transgenesis and somatic cell gene transfer methods, we defined discrete regions of the murine and human genes encoding myoglobin that are sufficient to confer muscle- and fiber type-specific expression to reporter genes. Mutational analysis confirms the importance of A/T-rich, MEF2-binding motifs in myoglobin gene regulation, as suggested by previous studies using different experimental approaches. In addition, we demonstrated a previously unsuspected role for an intragenic E-box motif as a negative regulatory element contributing to the tightly regulated variation in myoglobin gene expression among particular myofiber subtypes.

Myogenic differentiation of Mytilus larval cells in vitro

A myogenic differentiation program can be realized during the cultivation of Mytilus trossulus cells derived from larvae in premyogenic developmental stages. About 10-15% of cells in such cultures showed that they are capable of contracting actively. The shape of such cells and the high concentration of actin microfilaments indicate a similarity with smooth muscle cells. However, the pattern of contractile activity and the protein composition of these cells differ significantly from the corresponding characteristics of differentiated smooth muscle cells. The proportion between the main proteins of the thick fiber, paramyosin, and myosin in cultivated cells is far lower than in the muscles of larvae or adult molluscs. We also found that substrates with different adhesional characteristics may determine cell development towards one or the other phenotype. Cells attached to the collagen substrate, but not spread on it, had high proliferative potential; the collagen substrate, however, inhibited myogenic differentiation.

Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle.

Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.

Mapping of electrical muscle stimulation using MRI.

The purpose of this study was to map the pattern of muscle contractile activity elicited by electromyostimulation (EMS). A secondary interest was to determine whether EMS evoked a different pattern of contractile activity than voluntary (VOL) efforts. These objectives were addressed by examining the pattern and extent of contrast shift in magnetic resonance (MR) images after isometric actions of the left m. quadriceps of seven subjects had been elicited by EMS (1-s train of 500-microseconds sine wave pulses at 50 Hz) or by VOL means. For both conditions, five sets of 10 muscle actions were executed at each of the three force levels equal to 25, 50, and 75% of maximal VOL isometric torque. There were 1-s, 1.5-min, and 30-min rests between muscle actions, sets, and torque levels, respectively. Transaxial proton MR images (TR/TE = 2,000/30, 60) of m. quadriceps femoris were obtained with a 1.5-T imager at rest and after completion of the five sets of isometric actions at each force level. MR image contrast shift, as indicated by T2 values > 1 SD above the mean resting muscle T2, was calculated per pixel. Torque declined approximately 18% (P < 0.05) during each EMS set independent of the preset relative force level but recovered between sets. EMS increased T2 values above rest (29 +/- 0.2 to 36 +/- 0.5, P < 0.05) in regions of muscle dispersed throughout a given cross section. The pattern of muscle stimulation, as reflected by increased T2 values, varied markedly among subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiology of myometrial function: intercellular coupling and its role in uterine contractility

The mammalian uterus is composed of a preponderance of small smooth muscle cells usually aligned in two layers. The number of muscle cells in the human uterus at term is estimated at 200 billion, each minute fusiform cell measuring about 5–10μm in diameter and about 200μm in length. The main function of the uterus is to harbour the developing fetus during pregnancy and then to contract vigorously during labour to expel the products of conception. In order for the uterus to contract rhythmically and forcefully, a mechanism must exist to allow interaction between muscle cells in order to achieve synchronous activity. Phasic or cyclical patterns of contractile activity of the uterus cannot be accounted for by stimulation or inhibition from the nervous or endocrine systems. Since myometrial cells are dependent upon action potentials for their contractile processes, some system must be present between the muscle cells for the propagation of action potentials between them. The observation that gap junctions occur in large numbers between myometrial cells during parturition is thought to be significant in this regard and they are considered to play an essential role in parturition and in the control and co-ordination of uterine contractility. In this brief review, we will discuss the role of gap junctions in the modulation of myometrial contractility and the mechanisms that regulate their synthesis and permeability.

Myoelectric and Manometric Patterns of Human Rectosigmoid Colon in Irritable Bowel Syndrome and Diverticulosis

Rectosigmoid electric control activity and intraluminal pressure were measured in the fasting state and after a standard 3040-kJ meal in irritable bowel syndrome (IBS) patients (n = 41), diverticulosis patients (n = 15), and healthy controls (n = 13). Analysis of myoelectric and motor patterns was performed computer-based with home-made software. Spectral analysis (fast Fourier transform) and computer recognition of slow waves emulating visual scoring showed very similar slow-wave frequency patterns in all three groups. Calculation of contractile indices displayed a widely scattered variable of motility in all three groups without significant differences. IBS subgroups with different bowel patterns showed very similar frequencies of basic myoelectric rhythm and a considerable overlap of contractile activity without significant differences among the subgroups and compared with controls. Slow-wave rhythm seems unlikely to be the basis of disturbed motility in IBS and diverticular disease. A specific pattern of contractile activity was not detectable in either condition.

Metabolic specialization in fast and slow muscle fibers of the developing rat

Individual fibers of prospective fast (extensor digitorum longus; EDL) and slow (soleus) muscles of rats have been analyzed to determine the profiles of key energy-generating enzymes at successive stages of postnatal development. Mean activities of lactate dehydrogenase (LDH) and adenylokinase (AK), 2 enzymes associated with contractile function, are significantly different in the 2 fiber populations at birth; furthermore, wide variations in enzyme activities exist among the individual fibers. There is a progressive refinement of enzyme levels in the soleus into a more uniform fiber population, while the fibers in the EDL progressively diverge into 2 distinct phenotypes. Changes in EDL and soleus are punctuated by periods of rapid change, with the period between 10 and 21 d being most eventful. Generally, the maturation profiles of LDH and AK coincide with the transition from neonatal to adult fast myosins and closely reflect the timing of energy demands imposed by contractile activity patterns. In contrast, activities of the oxidative enzymes malate dehydrogenase and beta-hydroxyacyl CoA dehydrogenase are similar in both muscles at birth and steadily increase during the first 3 weeks, suggesting a progressive adaptation to the aerobic extrauterine environment. After 30 d, there are differential changes in the oxidative profiles of enzymes for fatty acid and glucose metabolism. The profiles follow dietary changes associated with weaning, which suggests a phenotypic dependence of neonatal muscle on the particular available energy substrate. All enzymes are low in all fibers of EDL and soleus at birth, indicating their modest metabolic capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Active site trapping of nucleotide by smooth and non-muscle myosins

The folded 10 S monomer conformation of smooth muscle myosin traps the hydrolysis products ADP and P i in its active sites. To test the significance of this, we have searched for equivalent trapping in other conformational and assembly states of avian gizzard and brush border myosins, using formycin triphosphate (FTP) as an ATP analogue. When myosin monomers were in the straight-tail 6 S conformation, the hydrolysis products were released at about 0·03 s −1. Adoption of the folded 10 S monomer conformation reduced this rate by more than 100-fold, effectively trapping the products FDP and P i in the active sites. This profound inhibition of product release occurred only on formation of the looped tail monomer conformation. In vitro-assembled myosin filaments released products at a comparable rate to free straight-tail 6 S monomers, and smooth muscle heavy meromyosin, which lacks the C-terminal two-thirds of the myosin tail, also did not trap the products in this way. Phosphorylation of the myosin regulatory light chain had no effect on the rate of product release from straight-tail 6 S myosin monomers or from myosin filaments. Rather, it allowed actin to accelerate product release. Phosphorylation acted also to destabilize the folded monomer conformation, causing the recruitment of molecules from the pool of folded monomers into the myosin filaments. The two processes of contraction and filament assembly are thus both controlled in vitro by light-chain phosphorylation. A similar linked control in vivo would allow the organization of myosin in the cell to adapt itself continuously to the pattern of contractile activity.

Measurement of resistance to flow across antroduodenal area during fasting.

Changes in antroduodenal resistance to flow may participate in the regulation of gastric emptying and duodenogastric reflux. Little is known, however, about the relationship between antroduodenal resistance and the physiological patterns of contractile activity in this area. We have developed an instrument that maintains an electronically regulated constant-pressure gradient of 2 mmHg across both ends of a flaccid cylinder positioned fluoroscopically across the pylorus. Because resistance bears a constant inverse relationship to flow at a fixed pressure gradient, changes in the recorded rate of airflow through the cylinder are a measure of antroduodenal resistance. In vitro studies showed that, under these conditions, airflow was a function of the diameter and length of the air path and the frequency and duration of external pressure waves greater than 2 mmHg. In vivo studies in four dogs examined the relationship between interdigestive phases of motor activity and variations in resistance exerted by the antroduodenal area. We found that flow rates varied markedly with each phase. Antroduodenal resistance was lowest during motor quiescence (phase I), rose gradually during irregular activity (phase II), and reached its peak during maximal contractile activity (phase III) (P less than 0.05). Resistance was similar for antegrade and retrograde flow. Additional studies suggested that the pyloric area contributes mostly to resistance during phase I, whereas duodenal resistance at least matches that of the pylorus during phase III.

Control of enzyme activities in individual myotubes cultured without nerve.

The activities of lactate dehydrogenase, malate dehydrogenase, phosphorylase, and adenylate kinase were measured in single myotubes dissected from primary cultures of rat skeletal muscle. For a given enzyme, activities among the spontaneously contracting cells varied as much as eightfold. When the myotubes were paralyzed with tetrodotoxin, the variability in enzyme levels was markedly decreased. These and other findings suggest that differences in enzyme levels among individual myotubes may arise as a result of differences in their pattern of contractile activity.

Patterns of spike burst spread and flow in the canine small intestine

We are describing a new method to illustrate the spread of spike bursts along the small intestine. Spike bursts migrate aborally in the longitudinal axis (from distances up to 30 to 40 cm at the same rate as slow waves). These were detected through the use of multiple closely and evenly spaced serosal electrodes in conscious dogs. Their occurrence is plotted with respect to electrode and time using a computer and printer. Patterns of contractile activity after fasting and feeding are illustrated. Outflow from an intraluminal cannula occurs in pulses preceded by spike burst activity in electrodes proximal to the cannula. This lends support to the concept that intestinal flow is accomplished by migrating ring contractions.

Somatostatin inhibits motilin-induced interdigestive contractile activity in the dog.

The interaction between motilin and somatostatin on gastrointestinal motor activity was studied in fasted, unanesthetized dogs. Contractions of the stomach, duodenum, jejunum, and ileum were recorded with extraluminal strain gage force transducers. Motilin initiated a pattern of contractile activity which closely resembled phase III of the interdigestive motor complex. Somatostatin delayed the onset of the motilin response and reduced motor activity in the stomach and the jejunum. During somatstatin infusion the motilin-induced contractile pattern did not migrate to the jejunum. The cycle of natural interdigestive motor complexes was also interrupted by somatostatin. Somatostatin alters natural and motilin-induced interdigestive migrating motor complexes of the canine gastrointestinal tract.

Developmental changes of the contractile activity and the drug sensitivity of smooth muscle of the alimentary tract of guinea pig.

The mechanical activity of the smooth muscle of guinea pig alimentary tract changed during fetal and postnatal development. At the F20 (fetus, body weight 20 g) stage of the fetus, the antrum, small intestinal and colonic preparations showed no spontaneous activity. After this stage, spontaneous activity occurred but the patterns of contractile activity of various regions of the alimentary tract differed from those of the adult. However, at later fetal stages (F50 or later), the mechanical patterns of various regions, except the lower region of colon, were similar to adult patterns. An excitatory response to acetylcholine was observed in all regions at the F20 stage but catecholamines were not effective at this stage. Responses to catecholamines appeared later than those to acetylcholine but they were not constant. During development of the colon, the excitatory effect of adrenaline was significant and the effect was blocked by phenoxybenzamine, and isoprenaline inhibited the spontaneous activity. However, sympathetic nerve stimulation at F70 inhibited the mechanical activity and propranolol blocked the inhibitory action of sympathetic nerves. These results indicate the co-existence of alpha-excitatory and beta-inhibitory receptors on the developing colonic smooth muscle cell membrane.

Studies on peptides. LV. Total synthesis of porcine motilin, a gastric motor activity stimulating polypeptide.

Synthesis of the docosapeptide corresponding to the newly revised sequence of porcine motilin, a gastric motor activity stimulating polypeptide, was accomplished. Synthetic peptide exhibited characteristic contractile activity patterns of the stomach and the duodenum in dogs, which were quite similar to those of the burst activity of these organs.