Passive Tension Development Research Articles

Effects of fasting on isolated murine skeletal muscle contractile function during acute hypoxia.

Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute hypoxia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct rodent hindlimb muscles that have well characterized differences in energetic efficiency (locomotory- extensor digitorum longus (EDL) and postural- soleus muscles) following a 24 hour fasting period that resulted in substantially reduced muscle carbohydrate supply. 180 mins of acute hypoxia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product-inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Fasting and the associated reduction of the available intracellular carbohydrate pool (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting resulted in greater passive tension development in both muscle types, which may have implications for the design of pre-clinical studies involving optimal timing of reperfusion or administration of precision therapeutics.

Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension.

We have previously shown that treatment with recombinant human neuregulin-1 (rhNRG-1) improves pulmonary arterial hypertension (PAH) in a monocrotaline (MCT)-induced animal model, by decreasing pulmonary arterial remodelling and endothelial dysfunction, as well as by restoring right ventricular (RV) function. Additionally, rhNRG-1 treatment showed direct myocardial anti-remodelling effects in a model of pressure loading of the RV without PAH. This work aimed to study the intrinsic cardiac effects of rhNRG-1 on experimental PAH and RV pressure overload, and more specifically on diastolic stiffness, at both the ventricular and cardiomyocyte level. We studied the effects of chronic rhNRG-1 treatment on ventricular passive stiffness in RV and LV samples from MCT-induced PAH animals and in the RV from animals with compensated and decompensated RV hypertrophy, through a mild and severe pulmonary artery banding (PAB). We also measured passive tension in isolated cardiomyocytes and quantified the expression of myocardial remodelling-associated genes and calcium handling proteins. Chronic rhNRG-1 treatment decreased passive tension development in RV and LV isolated from animals with MCT-induced PAH. This decrease was associated with increased phospholamban phosphorylation, and with attenuation of the expression of cardiac maladaptive remodelling markers. Finally, we showed that rhNRG-1 therapy decreased RV remodelling and cardiomyocyte passive tension development in PAB-induced RV hypertrophy animals, without compromising cardiac function, pointing to cardiac-specific effects in both hypertrophy stages. In conclusion, we demonstrated that rhNRG-1 treatment decreased RV intrinsic diastolic stiffness, through the improvement of calcium handling and cardiac remodelling signalling.

Sarcomere Lengthdependent Effects on the Ca2+-Troponin Regulation in Skinned Myocardial Fiber from Titin RBM20 Deletion Mice

The length dependent activation of the myofilaments has been considered the cellular basis underlying the Frank-Starling law of the heart trough dynamic and complex interplays between a multitude of thick- and thin-filament components. Among these components, both troponin and giant protein titin are likely key players, but the mechanism, by which the length dependent myofilament Ca2+ regulation is linked functionally to titin, is elusive. In this study we investigate the link using in situ FRET technique to monitor how the length dependent Ca2+-induced conformational change of the N-domain of cTnC within myocardium is modulated by alteration of titin compliance that directly determines the passive tension of myocardium. To achieve the objective, FRET donor and acceptor modified cTnC(13C/51C)AEDANS-DDPM was reconstituted into chemically-skinned myocardial fibers from wild-type mice and RBM20 deficient mice that expresses more compliant N2BA titin. The Ca2+-induced conformational change in cTnC under different conditions were quantitatively characterized using time-resolved FRET measurements. Our results from wild type myocardium showed that sarcomere length dependent enhancement of Ca2+-troponin regulation was found to be directly associated with strong crossbridge and it was diminished when the strong crossbridge was inhibited. When measurements were performed with skinned myocardial fibers from RBM20 deletion animals, the length dependent change was blunted. These results support that titin based passive tension development of myocardium is indeed involved in sarcomere length modulated Ca2+-troponin regulation and that the strong crossbridge plays an important role in linking the modulatory effect of titin compliance to Ca2+-troponin regulation.

Incompressible fluid plays a mechanical role in the development of passive muscle tension.

Over short time scales, muscle fibres maintain a nearly constant volume of intracellular fluid. This fluid is essential to normal biochemical function, but its role in determining the mechanical properties of muscle has been considered in only a few theoretical analyses. Here we investigate the mechanical role of fluid in a fundamental property of muscle, its development of passive tension in response to stretch. We test a model of muscle structure in which incompressible fluid directly influences passive tension by constraining the geometry of intramuscular connective tissues. This interaction is demonstrated using a simple physical model of muscle morphology comprising a fluid-filled bladder wrapped by helical fibres. The behaviour of the model is compared with that of isolated bullfrog muscle subjected to an osmotic perturbation of intracellular fluid volume. Increasing muscle volume by 40% resulted in 69% increased passive tension, occurring in a manner consistent with the behaviour of the model. These observations support the notion that the interaction of connective tissues with the muscle fibres they surround influences the mechanical behaviour of whole muscles, and highlight the role of fluid as a mechanical component of muscle.

Indirect evidence for elastic energy playing a role in limb recovery during toad hopping.

Elastic energy is critical for amplifying muscle power during the propulsive phase of anuran jumping. In this study, we use toads (Bufo marinus) to address whether elastic recoil is also involved after take-off to help flex the limbs before landing. The potential for such spring-like behaviour stems from the unusually flexed configuration of a toad's hindlimbs in a relaxed state. Manual extension of the knee beyond approximately 90° leads to the rapid development of passive tension in the limb as underlying elastic tissues become stretched. We hypothesized that during take-off, the knee regularly extends beyond this, allowing passive recoil to help drive limb flexion in mid-air. To test this, we used high-speed video and electromyography to record hindlimb kinematics and electrical activity in a hindlimb extensor (semimembranosus) and flexor (iliofibularis). We predicted that hops in which the knees extended further during take-off would require less knee flexor recruitment during recovery. Knees extended beyond 90° in over 80% of hops, and longer hops involved greater degrees of knee extension during take-off and more intense semimembranosus activity. However, knee flexion velocities during recovery were maintained despite a significant decrease in iliofibularis intensity in longer hops, results consistent with elastic recoil playing a role.

Human skeletal muscle biochemical diversity

The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability.

Biochemical diversity of human skeletal muscle

INTRODUCTIONThe molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain [MHC]), and mechanosensitive signaling (titin) are well studied in animals but less is known about their roles in humans.METHODS599 biopsies were obtained from 6 human cadaveric donors. Three assays were performed on each biopsy ‐ titin molecular weight determination, hydroxyproline content (a surrogate for collagen content), and MHC isoform distribution.RESULTSDiscriminant function analysis (DFA) showed that titin MW was the strongest predictive factor of anatomic region and muscle functional group. On average, human muscles had more slow myosin than lower mammals. Average %MHC‐1 of muscles in this study was 65% (compare to 6% for mouse, 8% for rat, and 19% for rabbit). Overall, larger titins were associated with faster muscles.DISCUSSIONThe finding that titin was the strongest discriminating factor for DFA with anatomic region and muscle functional group as grouping variables is unexpected; titin is currently primarily considered to be a signal transduction cascade activator or determinant of passive tension. The titin‐MHC‐1 relationship we observed is opposite to that previously observed in rabbits, where large titins were associated with slower muscles.

Biochemical Diversity of Human Skeletal Muscle

INTRODUCTIONThe molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain [MHC]), and mechanosensitive signaling (titin) are well studied in animals. We performed a comprehensive analysis of these components in human muscle to search for common themes and trends in the muscular organization of the human body.METHODS599 biopsies from 6 donors were obtained early postmortem. Three assays were performed on each biopsy - titin molecular weight determination (n=586), hydroxyproline content (a surrogate for collagen content) (n=599), and MHC isoform distribution (n=599).Muscles were analyzed individually and in functional groups. Analysis of variance (ANOVA) was used to compare individual muscles and discriminant function analysis (DFA) was used to determine which dependent variables were the best predictors of muscle group.RESULTSDFA demonstrated that titin MW was the strongest predictive factor of anatomic region and muscle functional group.On average, human muscles were very “slow” (i.e., had more slow- myosin than muscles of lower mammals). Average % MHC-1 of muscles in this study was 65% (compare to 6% for mouse, 8% for rat, and 19% for rabbit). Overall, larger titins were associated with faster muscles.DISCUSSION:The finding that titin was the strongest discriminating factor for DFA with anatomic region and muscle functional group as grouping variables is unexpected; titin is currently primarily considered to be a signal transduction cascade activator or determinant of passive tension. The idea that titin MW is a good predictor of muscle anatomic localization is previously unexplored and warrants further study.The titin-% MHC-1 relationship we observed is opposite to that previously reported in rabbits, where large titins were associated with slower muscles. This may represent a different design paradigm in human vs rabbit muscular organization.

Single Molecule Studies of a Titin Mutation Linked to Cardiac Disease

Recently, a mutation in the 10th immunoglobulin(Ig)-like domain in titin's elastic I-band was found in a family affected with arrhythmogenic cardiomyopathy (AC). AC is characterized by fibrofatty replacement of myocardium, which can lead to fatal ventricular arrhythmias. Titin is a gigantic sarcomeric protein that is responsible for passive tension development in stretched cardiac muscle. We investigated the effect that the AC-linked point mutation (T16I in Ig10) has on the mechanical and kinetic stability of Ig10 using single molecule force spectroscopy (AFM) and degradation assays. Our AFM data indicate that T16I Ig10 unfolds at a lower force than WT Ig10, which shows that it is mechanically less stable. We also performed force clamp and refolding experiments with AFM and found that the unfolding rate of T16I Ig10 is four times higher than WT Ig10 (.02/s vs. .005/s at zero force), but that this difference is further increased in a force-dependent manner; refolding rates were found to be similar. We also performed degradation assays with the protease tryspin to determine if the T16I mutation affects the highly-stable beta barrel tertiary structure typical of Ig domains. We found that T16I Ig10 has a greater proteolytic susceptibility compared to WT Ig10, and subsequent mass spectrometry analysis determined that the primary cleavage site in T16I Ig10 is the lysine residue that flanks T16I (K17). This strongly suggests that the disease-linked titin mutation disrupts the local structure of Ig10 in the vicinity of T16, which leaves Ig10 vulnerable to cleavage. Peptide bond breakage anywhere along titin's elastic region (which includes Ig10) would likely abolish titin's ability to generate force and lead to severe physiological responses.

The effects of PKCα phosphorylation on the extensibility of titin’s PEVK element

Post-translational modifications, along with isoform splicing, of titin determine the passive tension development of stretched sarcomeres. It was recently shown that PKCalpha phosphorylates two highly-conserved residues (S26 and S170) of the PEVK region in cardiac titin, resulting in passive tension increase. To determine how each phosphorylated residue affects myocardial stiffness, we generated three recombinant mutant PEVK fragments (S26A, S170A and S170A/S26A), each flanked by Ig domains. Single-molecule force spectroscopy shows that PKCalpha decreases the PEVK persistence length (from 0.99 to 0.68 nm); the majority of this decrease is attributable to phosphorylation of S26. Before PKCalpha, all three mutant PEVK fragments showed at least 40% decrease in persistence length compared to wildtype. Furthermore, Ig domain unfolding force measurements indicate that PEVK's flanking Ig domains are relatively unstable compared to other titin Ig domains. We conclude that phosphorylation of S26 is the primary mechanism through which PKCalpha modulates cardiac stiffness.

Single Molecule Analysis of PKC Phosphorylation of Titin's PEVK Domain

Titin's I-band region contains three spring-like domains that are primarily responsible for the development of passive tension in cardiac muscle. PKC phosphorylation targets one of these I-band domains_the PEVK region, which is rich in proline (P), glutamate (E), valine (V), and lysine (K). It has been shown that two serine residues within the PEVK are targeted by PKC phosphorylation, S26 and S170. We investigate the effects of PKC phosphorylation of these two residues on the single molecule level using force-extension curves generated by atomic force microscopy (AFM). We constructed four recombinant proteins: two PEVK single mutants (S26A and S170A), a PEVK double mutant (S26AS170A), and a wild-type PEVK segment. All constructs are flanked by immunoglobulin-like domains, Ig27 and Ig84, and the unfolding of these domains generates a single molecular “fingerprint”. The force-extension curve leading up to the first unfolding peak describes the force-extension relationship of the PEVK. Preliminary data suggests that mutating either serine residue alters PEVK resistance to extension, which is quantified by the molecule's persistence length (PL). Wild-type PEVK underwent a large decrease in its PL after phosphorylation by PKC (by ∼50%), and both single mutants have PLs similar to that of phosphorylated wild-type PEVK. Furthermore, phosphorylation of both single mutants resulted in a small PL decrease. Phosphorylation decreased PL for the S26A mutation by 16% (from 0.55 ± 0.02 to 0.46 ± 0.02 (mean ± SE)), and the serine-170 mutation PL by 11% (from 0.53 ± 0.04 to 0.47 ± 0.03). The double mutant was not affected by PKC (from 0.51 ± 0.04 to 0.51 ± 0.03). We conclude that both serines play a structural role in determining the relationship between longitudinal force and PEVK extension, and that this role is modulated through phosphorylation by PKC.

Passive tension of rat skeletal soleus muscle fibers: effects of unloading conditions.

In this work we studied changes in passive elastic properties of rat soleus muscle fibers subjected to 14 days of hindlimb unloading (HU). For this purpose, we investigated the titin isoform expression in soleus muscles, passive tension-fiber strain relationships of single fibers, and the effects of the thick filament depolymerization on passive tension development. The myosin heavy chain composition was also measured for all fibers studied. Despite a slow-to-fast transformation of the soleus muscles on the basis of their myosin heavy chain content, no modification in the titin isoform expression was detected after 14 days of HU. However, the passive tension-fiber strain relationships revealed that passive tension of both slow and fast HU soleus fibers increased less steeply with sarcomere length than that of control fibers. Gel analysis suggested that this result could be explained by a decrease in the amount of titin in soleus muscle after HU. Furthermore, the thick filament depolymerization was found to similarly decrease passive tension in control and HU soleus fibers. Taken together, these results suggested that HU did not change titin isoform expression in the soleus muscle, but rather modified muscle stiffness by decreasing the amount of titin.

Length dependence of tension generation in rat skinned cardiac muscle: role of titin in the Frank-Starling mechanism of the heart.

At the basis of the Frank-Starling mechanism is the intrinsic ability of cardiac muscle to produce active tension in response to stretch. Titin, a giant filamentous molecule involved in passive tension development, is intimately associated with the thick filament in the sarcomere. Titin may therefore contribute to active tension development by modulating the thick filament structure when the muscle is elongated. Rat skinned right ventricular trabeculae were used. Passive tension at a sarcomere length (SL) of 2.0 to 2.4 micrometer was decreased after treatment of the preparation with trypsin (0.25 microgram/mL) for 13 minutes in the relaxed state at 20 degrees C. This mild trypsin treatment degraded titin without affecting other major contractile proteins. The sarcomere structure was little affected by brief contractions in the trypsin-treated preparations. When SL was adjusted to the slack SL (1.9 micrometer), active tension was unaffected by trypsin under partial (pCa 5.55) and maximal (pCa 4.8) activation. At longer SLs, however, active tension was significantly (P<0.01) decreased after trypsin treatment at either pCa. The increase in active tension on reduction of interfilament lattice spacing, produced by dextran T-500 (molecular weight approximately 500 000), was not influenced by trypsin (SL 1.9 micrometer). In trypsin-treated preparations, the increase in active tension as a function of muscle diameter was nearly the same for lengthening and osmotic compression at the slack SL. The length-dependent activation in cardiac muscle, an underlying mechanism of the Frank-Starling law of the heart, is at the myofilament level, predominantly modulated by titin and interfilament lattice spacing changes.

Nonuniform elasticity of titin in cardiac myocytes: a study using immunoelectron microscopy and cellular mechanics

Titin (also known as connectin) is a muscle-specific giant protein found inside the sarcomere, spanning from the Z-line to the M-line. The I-band segment of titin is considered to function as a molecular spring that develops tension when sarcomeres are stretched (passive tension). Recent studies on skeletal muscle indicate that it is not the entire I-band segment of titin that behaves as a spring; some sections are inelastic and do not take part in the development of passive tension. To better understand the mechanism of passive tension development in the heart, where passive tension plays an essential role in the pumping function, we investigated titin's elastic segment in cardiac myocytes using structural and mechanical techniques. Single cardiac myocytes were stretched by various amounts and then immunolabeled and processed for electron microscopy in the stretched state. Monoclonal antibodies that recognize different titin epitopes were used, and the locations of the titin epitopes in the sarcomere were studied as a function of sarcomere length. We found that only a small region of the I-band segment of titin is elastic; its contour length is estimated at approximately 75 nm, which is only approximately 40% of the total I-band segment of titin. Passive tension measurements indicated that the fundamental determinant of how much passive tension the heart develops is the strain of titin's elastic segment. Furthermore, we found evidence that in sarcomeres that are slack (length, approximately 1.85 microns) the elastic titin segment is highly folded on top of itself. Based on the data, we propose a two-stage mechanism of passive tension development in the heart, in which, between sarcomere lengths of approximately 1.85 microns and approximately 2.0 microns, titin's elastic segment straightens and, at lengths longer than approximately 2.0 microns, the molecular domains that make up titin's elastic segment unravel. Sarcomere shortening to lengths below slack (approximately 1.85 microns) also results in straightening of the elastic titin segment, giving rise to a force that opposes shortening and that tends to bring sarcomeres back to their slack length.

Interplay between passive tension and strong and weak binding cross-bridges in insect indirect flight muscle. A functional dissection by gelsolin-mediated thin filament removal.

The interplay between passive and active mechanical properties of indirect flight muscle of the waterbug (Lethocerus) was investigated. A functional dissection of the relative contribution of cross-bridges, actin filaments, and C filaments to tension and stiffness of passive, activated, and rigor fibers was carried out by comparing mechanical properties at different ionic strengths of sarcomeres with and without thin filaments. Selective thin filament removal was accomplished by treatment with the actin-severving protein gelsolin. Thin filament, removal had no effect on passive tension, indicating that the C filament and the actin filament are mechanically independent and that passive tension is developed by the C filament in response to sarcomere stretch. Passive tension increased steeply with sarcomere length until an elastic limit was reached at only 6-7% sarcomere extension, which corresponds to an extension of 350% of the C filament. The passive tension-length relation of insect flight muscle was analyzed using a segmental extension model of passive tension development (Wang, K, R. McCarter, J. Wright, B. Jennate, and R Ramirez-Mitchell. 1991. Proc. Natl. Acad. Sci. USA. 88:7101-7109). Thin filament removal greatly depressed high frequency passive stiffness (2.2 kHz) and eliminated the ionic strength sensitivity of passive stiffness. It is likely that the passive stiffness component that is removed by gelsolin is derived from weak-binding cross-bridges, while the component that remains is derived from the C filament. Our results indicate that a significant number of weak-binding cross-bridges exist in passive insect muscle at room temperature and at an ionic strength of 195 mM. Analysis of rigor muscle indicated that while rigor tension is entirely actin based, rigor stiffness contains a component that resists gelsolin treatment and is therefore likely to be C filament based. Active tension and active stiffness of unextracted fibers were directly proportional to passive tension before activation. Similarly, passive stiffness due to weak bridges also increased linearly with passive tension, up to a limit. These correlations lead us to propose a stress-activation model for insect flight muscle in which passive tension is a prerequisite for the formation of both weak-binding and strong-binding cross-bridges.

A comparative study of the supramolecular structure of frog sartorius and dorsal semitendinosus muscle

This report describes a comparative X-ray diffraction study of the supramolecular structure of frog sartorius and semitendinosus muscles. For sarcomere lengths of 2.7 μm and below the X-ray diffraction diagrams of each muscle type are very similar; the only differences being that the diffraction diagram for semitendinosus muscles exhibit the presence of a broad diffraction band or a cluster of diffraction orders at a spacing of ca. 230.0 nm and, also, they lack a periodicity of ca. 102.0 nm. For sarcomere lengths greater than 2.7 μm disruption of the sarcomere from sartorius muscle occurs as seen by the loss of sampling in the diffraction diagram. The semitendinosus muscle can be stretched to much longer lengths (in excess of 3.0 μm) before a loss of sampling is detected. The data also shows that in the case of the semitendinosus muscle for long sarcomere lengths transverse bands of mass are able to move without retaining a defined distance to either the Z or the M lines. This is not observed in the case of the sartorius muscle. Thus, at resolutions between ca. 3.6 μm and 7.50 nm significant ultrastructural differences between these two muscles are apparent. The data suggest that the ability of these mass bands to move may be responsible for the differences in the development of passive tension exhibited by these two muscles.

Jejunal circular muscle motility is decreased in nematode-infected rat

Jejunal circular muscle motility was studied in vitro in rats 8–10 days after inoculation with the inflammation-inducing nematode Nippostrongylus brasiliensis. The passive properties of the muscle, i.e., the development of passive tension and the optimal amount of stretch for active contractions, were unchanged by infection. Infection decreased the development of active resting tension, spontaneous contractions, muscle contraction to muscarinic receptor activation, and direct electrical stimulation. Relaxation to β-adrenergic stimulation was also decreased in tissues from infected animals. Response to cholinergic stimulation, spontaneous contractions, and active resting tension were completely dependent on extracellular calcium. The dominant response to electrical stimulation of intrinsic nerves was relaxation in control tissue and contraction in tissue from infected rats. In the presence of atropine, all tissues from control rats but only 33% of the tissues from infected rats relaxed, suggesting a marked difference in functional inhibitory innervation. The inflammation may have either decreased the circular muscle responsiveness to the inhibitory transmitter or decreased the release of this transmitter. Thus, a nematode infection produces decreased responsiveness of the intestinal circular muscle to both contracting and relaxing stimuli and causes a reduction in functional inhibitory innervation in this layer. These changes suggest mechanisms for the reduction of intestinal transit observed after some nematode infections.

Physiological mechanisms of vocal frequency control: The role of tension

Control of fundamental frequency by the human voice may be accomplished using a variety of physiological mechanisms. Most of these mechanisms are myoelastic and include the length, mass, and longitudinal tension of the vocal folds. In this paper, a review of some of the data concerning the mechanisms for the creation of tension in the vocal folds is presented. The physiological mechanisms for the development of passive tension are reviewed and the potential contribution of passive tension in the control of fundamental frequency is discussed. Some of the mechanisms for the development of active muscle tension are described and the biomechanical characteristics of muscle are considered in the effort to explain the physiological control of fundamental frequency in the human voice Control of fundamental frequency by the human voice may be accomplished using a variety of physiological mechanisms. Most of these mechanisms are myoelastic and include the length, mass, and longitudinal tension of the vocal folds. In this paper, a review of some of the data concerning the mechanisms for the creation of tension in the vocal folds is presented. The physiological mechanisms for the development of passive tension are reviewed and the potential contribution of passive tension in the control of fundamental frequency is discussed. Some of the mechanisms for the development of active muscle tension are described and the biomechanical characteristics of muscle are considered in the effort to explain the physiological control of fundamental frequency in the human voice ErratumJournal of VoiceVol. 3Issue 2Preview Full-Text PDF

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure: A physiologic assessment

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H 2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.

Electrical and mechanical properties of the closer muscle of the Alaskan king crab Paralithodes camtschatica

1. 1. The Alaskan king crab, Paralithodes camtschatica, is characterized by very large muscle fibers—up to 4 mm dia. in the meropodite. 2. 2. The closer muscle is innervated by two excitor axons. Stimulation of the phasic axon elicits large, weakly facilitating junction potentials (j.p.'s) in proximal fiber, small strongly facilitating j.p.'s in central fibers and small j.p.'s in distal fibers which exhibit variable facilitation. Single stimulation of the phasic axon results in a twitch. 3. 3. Stimulation of the tonic axon results in medium-size, facilitating j.p.'s in distal fibers and small, strongly facilitating j.p.'s in central fibers. It does not innervate proximal fibers and never elicits a twitch. 4. 4. Sarcomere size is uniform (4–6 μ) for fibers observed in all portions of the closer muscle. Rise time (90–110 msec) and half-decay time (150–200 msec) for contraction of proximal, central and distal fibers are similar for direct stimulation to isolated fibers. 5. 5. Length-tension curves of single fibers show development of passive tension before the peak of active tension. 6. 6. An inhibitory axon was found in only a few cases; it fatigued rapidly. Application of 10 −5 M GABA reversibly reduced the size of phasic j.p.'s.