Force Depression in the Drosophila Jump Muscle

Force Depression ◽

Dependent Behavior ◽

The depression of isometric force after active shortening, termed force depression (FD), is a well-accepted characteristic of skeletal muscle that has been demonstrated in both whole muscle [1,3] and single-fiber preparations [1,2]. Although this history-dependent behavior has been observed experimentally for over 70 years, its underlying mechanism(s) remain unknown. Drosophila melangastor, commonly known as the fruit fly, is a well established, comprehensively understood, and genetically manipulable animal model. Furthermore, Drosophila have proved to be an accurate model species for studying muscle mechanics, and the Tergal Depressor of the Trochanter (TDT), or jump muscle, has most precisely resembled the mechanics of mammalian skeletal muscle [4]. Due to the structural and phenomenological similarities of the TDT muscle to skeletal muscle, in addition to the potential use of genetic mutations in fly models, it is extremely advantageous to investigate the presence of history dependent phenomenon in the TDT. If such phenomena are present, further investigation utilizing different myosin and actin isoforms to study the underlying mechanism(s) could produce new insight into this history-dependent phenomenon, otherwise impossible to elucidate using current experimental models. Thus, it is the goal of this study to determine the presence and degree of FD in the TDT muscle of wild type Drosophila.

Force Recovery After Activated Stretching in Whole Skeletal Muscle: Transient Aspects of Force Enhancement

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-193222 ◽

2008 ◽

Author(s):

Ryan A. Koppes ◽

David T. Corr

Keyword(s):

Skeletal Muscle ◽

Steady State ◽

Isometric Force ◽

Underlying Mechanism ◽

Mechanical Work ◽

Force Enhancement ◽

Transient Phenomena ◽

Force Depression ◽

Force Relaxation ◽

In Situ Experiments

The enhancement of isometric force after active stretching is a well-accepted and demonstrated characteristic of skeletal muscle in both whole muscle [1,2] and single-fiber preparations [1,3], but its mechanisms remain unknown. Although traditionally analyzed at steady-state, transient phenomena caused, at least in part, by cross-bridge kinetics may provide novel insight into the mechanisms associated with force enhancement (FE). In order to identify the transient aspects of FE and its relation to stretching speed, stretching amplitude, and muscle mechanical work, a post hoc analysis of in situ experiments in soleus muscle tendon units of anesthetized cats [2] was conducted. The period immediately following stretching, at which the force returns to steady-state, was fit using an exponential decay function. The aims of this study were to analyze and quantify the effects of stretching amplitude, stretching speed, and muscle mechanical work on steady-state force enhancement (FEss) and transient force relaxation rate after active stretching. The results of this study were interpreted with respect to prior force depression (FD) experiments [4], to identify if the two phenomena exhibited similar transient and steady-state behaviors, and thus could be described by the same underlying mechanism(s).

A new experimental model to study force depression: the Drosophila jump muscle

10.1152/japplphysiol.01029.2013 ◽

2014 ◽

Vol 116 (12) ◽

pp. 1543-1550 ◽

Cited By ~ 3

Author(s):

Ryan A. Koppes ◽

Douglas M. Swank ◽

David T. Corr

Keyword(s):

Steady State ◽

Experimental Model ◽

Fiber Length ◽

Isometric Force ◽

Underlying Mechanism ◽

Force Depression ◽

Force Recovery ◽

Sarcomere Proteins ◽

Initial Force

Force depression (FD) is a decrease in isometric force following active muscle shortening. Despite being well characterized experimentally, its underlying mechanism remains unknown. To develop a new, genetically manipulatable experimental model that would greatly improve our ability to study the underlying mechanism(s) of FD, we tested the Drosophila jump muscle for classical FD behavior. Steady-state force generation following active shortening decreased by 2, 8, and 11% of maximum isometric force with increasing shortening amplitudes of 5, 10, and 20% of optimal fiber length, and decreased by 11, 8, and 5% with increasing shortening velocities of 4, 20, and 200% of optimal fiber length per second. These steady-state FD (FDSS) characteristics of Drosophila jump muscle mimic those observed in mammalian skeletal muscle. A double exponential fit of transient force recovery following shortening identified two separate phases of force recovery: a rapid initial force redevelopment, and a slower recovery toward steady state. This analysis showed the slower rate of force redevelopment to be inversely proportional to the amount of FDSS, while the faster rate did not correlate with FDSS. This suggests that the mechanism behind the slower, most likely cross-bridge cycling rate, influences the amount of FDSS. Thus the jump muscle, when coupled with the genetic mutability of its sarcomere proteins, offers a unique and powerful experimental model to explore the underlying mechanism behind FD.

Transient and Steady-State Force Enhancement in the Drosophila Jump Muscle

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80455 ◽

2012 ◽

Author(s):

Ryan A. Koppes ◽

Douglas M. Swank ◽

David T. Corr

Keyword(s):

Steady State ◽

Isometric Force ◽

Recovery Period ◽

Underlying Mechanism ◽

Clear Correlation ◽

Force Enhancement ◽

Force Depression ◽

Force Recovery ◽

State Force ◽

The increase of isometric force after active lengthening, termed force enhancement (FE), is a well-accepted characteristic of skeletal muscle that has been demonstrated in both whole muscle [1,3] and single-fiber preparations [1,2]. The amount of FE increases with increasing amplitudes of stretch, yet no clear correlation between FE and the rate stretch has been demonstrated [2]. Although this behavior has been observed experimentally for over 70 years, its underlying mechanism(s) remain unknown. Furthermore, most studies of FE have been limited to steady-state (FESS) observations [1–3], whereas clues to the underlying mechanism(s) may very well exist in the transient force recovery period following an active stretch, as seen in another history-dependent phenomenon, force depression [4].

In vivo supraspinatus muscle contractility and architecture in rabbit

10.1152/japplphysiol.00609.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1405-1412

Author(s):

Sydnee A. Hyman ◽

Mackenzie B. Norman ◽

Shanelle N. Dorn ◽

Shannon N. Bremner ◽

Mary C. Esparza ◽

...

Keyword(s):

Skeletal Muscle ◽

Isometric Force ◽

Muscle Physiology ◽

Improved Method ◽

Muscle Contractility ◽

Supraspinatus Muscle ◽

Contractile Stress ◽

Maximum Isometric Force

We introduce an improved method to assess rabbit supraspinatus muscle physiology. Maximum isometric force measured for the rabbit supraspinatus was dramatically greater than previous reports in the literature. Consequently, the isometric contractile stress reported is almost 10 times greater than previous reports of rabbit supraspinatus, but similar to available literature of other mammalian skeletal muscle. We show that previous reports of peak supraspinatus isometric force were subphysiological by ∼90%

The influence of training-induced sarcomerogenesis on the history dependence of force

Journal of Experimental Biology ◽

10.1242/jeb.218776 ◽

2020 ◽

Vol 223 (15) ◽

pp. jeb218776 ◽

Cited By ~ 3

Author(s):

Jackey Chen ◽

Parastoo Mashouri ◽

Stephanie Fontyn ◽

Mikella Valvano ◽

Shakeap Elliott-Mohamed ◽

...

Keyword(s):

Extensor Digitorum Longus ◽

Isometric Force ◽

Muscle Length ◽

Force Enhancement ◽

Active Muscle ◽

Training Groups ◽

Force Depression ◽

Residual Force ◽

Residual Force Enhancement ◽

ABSTRACTThe increase or decrease in isometric force following active muscle lengthening or shortening, relative to a reference isometric contraction at the same muscle length and level of activation, are referred to as residual force enhancement (rFE) and residual force depression (rFD), respectively. The purpose of these experiments was to investigate the trainability of rFE and rFD on the basis of serial sarcomere number (SSN) alterations to history-dependent force properties. Maximal rFE/rFD measures from the soleus and extensor digitorum longus (EDL) of rats were compared after 4 weeks of uphill or downhill running with a no-running control. SSN adapted to the training: soleus SSN was greater with downhill compared with uphill running, while EDL demonstrated a trend towards more SSN for downhill compared with no running. In contrast, rFE and rFD did not differ across training groups for either muscle. As such, it appears that training-induced SSN adaptations do not modify rFE or rFD at the whole-muscle level.

Force recovery after activated shortening in whole skeletal muscle: transient and steady-state aspects of force depression

10.1152/japplphysiol.00509.2004 ◽

2005 ◽

Vol 99 (1) ◽

pp. 252-260 ◽

Cited By ~ 15

Author(s):

David T. Corr ◽

Walter Herzog

Keyword(s):

Skeletal Muscle ◽

Steady State ◽

Isometric Force ◽

Mechanical Work ◽

Transient Phenomena ◽

Cross Bridge ◽

Force Depression ◽

In Situ Experiments ◽

Force Recovery ◽

Cross Bridges

The depression of isometric force after active shortening is a well-accepted characteristic of skeletal muscle, yet its mechanisms remain unknown. Although traditionally analyzed at steady state, transient phenomena caused, at least in part, by cross-bridge kinetics may provide novel insight into the mechanisms associated with force depression (FD). To identify the transient aspects of FD and its relation to shortening speed, shortening amplitude, and muscle mechanical work, in situ experiments were conducted in soleus muscle-tendon units of anesthetized cats. The period immediately after shortening, in which force recovers toward steady state, was fit by using an exponential recovery function ( R2 > 0.99). Statistical analyses revealed that steady-state FD (FDss) increased with shortening amplitude and mechanical work. This FDss increase was always accompanied by a significant decrease in force recovery rate. Furthermore, a significant reduction in stiffness was observed after all activated shortenings, presumably because of a reduced proportion of attached cross bridges. These results were interpreted with respect to the two most prominent proposed mechanisms of force depression: sarcomere length nonuniformity theory ( 7 , 32 ) and a stress-induced inhibition of cross-bridge binding in the newly formed actin-myosin overlap zone ( 14 , 28 ). We hypothesized that the latter could describe both steady-state and transient aspects of FD using a single scalar variable, the mechanical work done during shortening. As either excursion (overlap) or force (stress) is increased, mechanical work increases, and cross-bridge attachment would become more inhibited, as supported by this study in which an increase in mechanical work resulted in a slower recovery to a more depressed steady-state force.

Modelling extracellular matrix and cellular contributions to whole muscle mechanics

PLoS ONE ◽

10.1371/journal.pone.0249601 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249601

Author(s):

Ryan N. Konno ◽

Nilima Nigam ◽

James M. Wakeling

Keyword(s):

Skeletal Muscle ◽

Muscle Tissue ◽

Muscle Mechanics ◽

Skeletal Muscle Tissue ◽

Elastic Response ◽

Muscle Fibres ◽

Heterogeneous Structure ◽

Tissue Fluid ◽

Material Parameters ◽

Skeletal muscle tissue has a highly complex and heterogeneous structure comprising several physical length scales. In the simplest model of muscle tissue, it can be represented as a one dimensional nonlinear spring in the direction of muscle fibres. However, at the finest level, muscle tissue includes a complex network of collagen fibres, actin and myosin proteins, and other cellular materials. This study shall derive an intermediate physical model which encapsulates the major contributions of the muscle components to the elastic response apart from activation-related along-fibre responses. The micro-mechanical factors in skeletal muscle tissue (eg. connective tissue, fluid, and fibres) can be homogenized into one material aggregate that will capture the behaviour of the combination of material components. In order to do this, the corresponding volume fractions for each type of material need to be determined by comparing the stress-strain relationship for a volume containing each material. This results in a model that accounts for the micro-mechanical features found in muscle and can therefore be used to analyze effects of neuro-muscular diseases such as cerebral palsy or muscular dystrophies. The purpose of this study is to construct a model of muscle tissue that, through choosing the correct material parameters based on experimental data, will accurately capture the mechanical behaviour of whole muscle. This model is then used to look at the impacts of the bulk modulus and material parameters on muscle deformation and strain energy-density distributions.

A myosin-based mechanism for stretch activation and its possible role revealed by varying phosphate concentration in fast and slow mouse skeletal muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.00206.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1143-C1152 ◽

Cited By ~ 1

Author(s):

Chad R. Straight ◽

Kaylyn M. Bell ◽

Jared N. Slosberg ◽

Mark S. Miller ◽

Douglas M. Swank

Keyword(s):

Skeletal Muscle ◽

Isometric Force ◽

Muscle Fibers ◽

Muscle Length ◽

Power Stroke ◽

Stretch Activation ◽

Force Ratio ◽

Slow Twitch ◽

Fast Twitch

Stretch activation (SA) is a delayed increase in force following a rapid muscle length increase. SA is best known for its role in asynchronous insect flight muscle, where it has replaced calcium’s typical role of modulating muscle force levels during a contraction cycle. SA also occurs in mammalian skeletal muscle but has previously been thought to be too low in magnitude, relative to calcium-activated (CA) force, to be a significant contributor to force generation during locomotion. To test this supposition, we compared SA and CA force at different Pi concentrations (0–16 mM) in skinned mouse soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscle fibers. CA isometric force decreased similarly in both muscles with increasing Pi, as expected. SA force decreased with Pi in EDL (40%), leaving the SA to CA force ratio relatively constant across Pi concentrations (17–25%). In contrast, SA force increased in soleus (42%), causing a quadrupling of the SA to CA force ratio, from 11% at 0 mM Pi to 43% at 16 mM Pi, showing that SA is a significant force modulator in slow-twitch mammalian fibers. This modulation would be most prominent during prolonged muscle use, which increases Pi concentration and impairs calcium cycling. Based upon our previous Drosophila myosin isoform studies and this work, we propose that in slow-twitch fibers a rapid stretch in the presence of Pi reverses myosin’s power stroke, enabling quick rebinding to actin and enhanced force production, while in fast-twitch fibers, stretch and Pi cause myosin to detach from actin.

Shortening-induced residual force depression in humans

10.1152/japplphysiol.00931.2018 ◽

2019 ◽

Vol 126 (4) ◽

pp. 1066-1073 ◽

Cited By ~ 10

Author(s):

Jackey Chen ◽

Daniel Hahn ◽

Geoffrey A. Power

Keyword(s):

Positive Relationship ◽

Isometric Force ◽

Muscle Length ◽

Experimental Models ◽

Force Depression ◽

Current Review ◽

Isometric Muscle Contraction ◽

Residual Force ◽

Muscle Groups ◽

Isometric Muscle

When an isometric muscle contraction is immediately preceded by an active shortening contraction, a reduction in steady-state isometric force is observed relative to an isometric reference contraction at the same muscle length and level of activation. This shortening-induced reduction in isometric force, termed “residual force depression” (rFD), has been under investigation for over a half century. Various experimental models have revealed the positive relationship between rFD and the force and displacement performed during shortening, with rFD values ranging from 5 to 39% across various muscle groups, which appears to be due to a stress-induced inhibition of cross-bridge attachments. The current review will discuss the findings of rFD in humans during maximal and submaximal contractions.

Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00189.2013 ◽

2013 ◽

Vol 305 (3) ◽

pp. R281-R290 ◽

Cited By ~ 13

Author(s):

Michael Nyberg ◽

Baraa K. Al-Khazraji ◽

Stefan P. Mortensen ◽

Dwayne N. Jackson ◽

Christopher G. Ellis ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Muscle Blood Flow ◽

Gluteus Maximus ◽

Underlying Mechanism ◽

Experimental Models ◽

Muscle Contractions ◽

Rat Skeletal Muscle ◽

Vasodilator Effect ◽

Exercise Hyperemia

During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1–10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ∼60% and ∼40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation.