scholarly journals Myosin cross-bridge kinetics slow at longer muscle lengths during isometric contractions in intact soleus from mice

2021 ◽  
Vol 288 (1950) ◽  
Author(s):  
Axel J. Fenwick ◽  
David C. Lin ◽  
Bertrand C. W. Tanner
Keyword(s):  
Single Molecule ◽  
Muscle Function ◽  
Molecular Level ◽  
Force Production ◽  
Muscle Length ◽  
Single Fibre ◽  
Energy Utilization ◽  
Multi Scale ◽  
Cross Bridge ◽  
Whole Muscle

Muscle contraction results from force-generating cross-bridge interactions between myosin and actin. Cross-bridge cycling kinetics underlie fundamental contractile properties, such as active force production and energy utilization. Factors that influence cross-bridge kinetics at the molecular level propagate through the sarcomeres, cells and tissue to modulate whole-muscle function. Conversely, movement and changes in the muscle length can influence cross-bridge kinetics on the molecular level. Reduced, single-molecule and single-fibre experiments have shown that increasing the strain on cross-bridges may slow their cycling rate and prolong their attachment duration. However, whether these strain-dependent cycling mechanisms persist in the intact muscle tissue, which encompasses more complex organization and passive elements, remains unclear. To investigate this multi-scale relationship, we adapted traditional step-stretch protocols for use with mouse soleus muscle during isometric tetanic contractions, enabling novel estimates of length-dependent cross-bridge kinetics in the intact skeletal muscle. Compared to rates at the optimal muscle length ( L o ), we found that cross-bridge detachment rates increased by approximately 20% at 90% of L o (shorter) and decreased by approximately 20% at 110% of L o (longer). These data indicate that cross-bridge kinetics vary with whole-muscle length during intact, isometric contraction, which could intrinsically modulate force generation and energetics, and suggests a multi-scale feedback pathway between whole-muscle function and cross-bridge activity.

The effects of pH on force and stiffness development in mouse muscles

1987 ◽  
Vol 65 (8) ◽  
pp. 1798-1801 ◽  
Author(s):  
J. M. Renaud ◽  
R. B. Stein ◽  
T. Gordon
Keyword(s):  
High Frequency ◽  
Small Amplitude ◽  
Force Production ◽  
Muscle Length ◽  
Low Ph ◽  
Muscle Stiffness ◽  
Average Force ◽  
Cross Bridge ◽  
Effects Of Ph ◽  
Cross Bridges

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (<0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.

scholarly journals Chemical energetics of force development, force maintenance, and relaxation in mammalian smooth muscle.

1980 ◽  
Vol 76 (5) ◽  
pp. 609-629 ◽  
Author(s):  
M J Siegman ◽  
T M Butler ◽  
S U Mooers ◽  
R E Davies
Keyword(s):  
Average Rate ◽  
Muscle Length ◽  
High Energy ◽  
Energy Utilization ◽  
High Rate ◽  
Force Development ◽  
Cross Bridge ◽  
Force Maintenance ◽  
Initial Force ◽  
Work Done

High-energy phosphate utilization (delta approximately P) associated with force development, force maintenance, and relaxation has been determined during single isometric tetani in the rabbit taenia coli. ATP resynthesis from glycolysis and respiration was stopped without deleterious effects on the muscle. At 18 degrees C and a muscle length of 95% l0, the resting rate of energy utilization is 1.8 +/- 0.2 nmol/g . s-1, or 0.85 +/- 0.2 mmol approximately P/mol of total creatine (Ct) . s-1, where Ct = 2.7 mumol/g wet wt. During the initial 25 s of stimulation when force is developed, the average rate of delta approximately P was -8.2 +/- 0.8 mmol/mol Ct . s-1, some four times greater than during the subsequent 35 s of force maintenance, when the rate was -2.0 +/- 0.6 mmol approximately P/mol Ct . s-1. The energy cost of force redevelopment (0 to 95% P0) after a quick release from the peak of a tetanus is very low compared with the initial force development. Therefore, the high rate of energy utilization during force development is not due only to internal work done against the series elasticity nor to any high rate of cross-bridge cycling inherently associated with force development. The high economy of force maintenance compared with other muscle types is undoubtedly due to a slower cross-bridge cycle time. The energy utilization during 45 s of relaxation was not statistically significant, and integral of Pdt/delta approximately P was higher during relaxation than during force maintenance in the stimulated muscle.

The origin of passive force enhancement in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. C74-C78 ◽  
Author(s):  
V. Joumaa ◽  
D. E. Rassier ◽  
T. R. Leonard ◽  
W. Herzog
Keyword(s):  
Calcium Concentration ◽  
Force Production ◽  
Primary Source ◽  
Passive Force ◽  
Active Force ◽  
Force Enhancement ◽  
Bridge Formation ◽  
Calcium Dependent ◽  
Cross Bridge ◽  
High Calcium

The aim of the present study was to test whether titin is a calcium-dependent spring and whether it is the source of the passive force enhancement observed in muscle and single fiber preparations. We measured passive force enhancement in troponin C (TnC)-depleted myofibrils in which active force production was completely eliminated. The TnC-depleted construct allowed for the investigation of the effect of calcium concentration on passive force, without the confounding effects of actin-myosin cross-bridge formation and active force production. Passive forces in TnC-depleted myofibrils ( n = 6) were 35.0 ± 2.9 nN/ μm2 when stretched to an average sarcomere length of 3.4 μm in a solution with low calcium concentration (pCa 8.0). Passive forces in the same myofibrils increased by 25% to 30% when stretches were performed in a solution with high calcium concentration (pCa 3.5). Since it is well accepted that titin is the primary source for passive force in rabbit psoas myofibrils and since the increase in passive force in TnC-depleted myofibrils was abolished after trypsin treatment, our results suggest that increasing calcium concentration is associated with increased titin stiffness. However, this calcium-induced titin stiffness accounted for only ∼25% of the passive force enhancement observed in intact myofibrils. Therefore, ∼75% of the normally occurring passive force enhancement remains unexplained. The findings of the present study suggest that passive force enhancement is partly caused by a calcium-induced increase in titin stiffness but also requires cross-bridge formation and/or active force production for full manifestation.

scholarly journals Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction

2016 ◽  
Vol 311 (2) ◽  
pp. E293-E301 ◽  
Author(s):  
Laura A. A. Gilliam ◽  
Daniel S. Lark ◽  
Lauren R. Reese ◽  
Maria J. Torres ◽  
Terence E. Ryan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Chemotherapy ◽  
Protein Oxidation ◽  
Muscle Function ◽  
Contractile Function ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Dysfunction ◽  
Whole Muscle ◽  
Loss Of Strength ◽  
Mitochondrial Respiratory

The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2. We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction.

Molecular Motors: Force and Movement Generated by Single Myosin II Molecules

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 213-218 ◽  
Author(s):  
Caspar Rüegg ◽  
Claudia Veigel ◽  
Justin E. Molloy ◽  
Stephan Schmitz ◽  
John C. Sparrow ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Force Production ◽  
Myosin Isoforms ◽  
Single Molecule Level ◽  
Recent Developments ◽  
Muscle Myosin

Muscle myosin II is an ATP-driven, actin-based molecular motor. Recent developments in optical tweezers technology have made it possible to study movement and force production on the single-molecule level and to find out how different myosin isoforms may have adapted to their specific physiological roles.

Selected Contribution: Effect of chronic passive length change on airway smooth muscle length-tension relationship

2001 ◽  
Vol 90 (2) ◽  
pp. 734-740 ◽  
Author(s):  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Force Production ◽  
Muscle Length ◽  
Electrical Field Stimulation ◽  
Length Change ◽  
Electrical Field ◽  
Optimal Length ◽  
Active Length ◽  
Reference Length ◽  
Relationship Of

The ability of rabbit trachealis to undergo plastic adaptation to chronic shortening or lengthening was assessed by setting the muscle preparations at three lengths for 24 h in relaxed state: a reference length in which applied force was ∼1–2% of maximal active force (Po) and lengths considerably shorter and longer than the reference. Passive and active length-tension ( L-T) curves for the preparations were then obtained by electrical field stimulation at progressively increasing muscle length. Classically shaped L-T curves were obtained with a distinct optimal length ( L o) at which Podeveloped; however, both the active and passive L-T curves were shifted, whereas Po remained unchanged. L o was 72% and 148% that of the reference preparations for the passively shortened and lengthened muscles, respectively. The results suggest that chronic narrowing of the airways could induce a shift in the L-T relationship of smooth muscle, resulting in a maintained potential for maximal force production.

scholarly journals Muscle Length is a Determinant of Cross-Bridge Cycling Rate in Intact Cardiac Trabeculae: Studies from Rodents to Humans

2013 ◽  
Vol 104 (2) ◽  
pp. 315a-316a
Author(s):  
Nima Milani-Nejad ◽  
Ying Xu ◽  
Jonathan P. Davis ◽  
Kenneth S. Campbell ◽  
George S. Billman ◽  
...  
Keyword(s):  
Muscle Length ◽  
Cycling Rate ◽  
Cross Bridge

scholarly journals The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium

2015 ◽  
Vol 309 (12) ◽  
pp. H2077-H2086 ◽  
Author(s):  
Nima Milani-Nejad ◽  
Benjamin D. Canan ◽  
Mohammad T. Elnakish ◽  
Jonathan P. Davis ◽  
Jae-Hoon Chung ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Muscle Length ◽  
Human Myocardium ◽  
Force Frequency ◽  
Heart Failure Patients ◽  
Cycling Rate ◽  
Physiological Conditions ◽  
Cross Bridge ◽  
The Right

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing ( n = 9) and failing ( n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae ( n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization ( P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment ( ktr) in both nonfailing and failing myocardium ( P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length ( P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/d t slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients.

The EMG-force relationship of the cat soleus muscle and its association with contractile conditions during locomotion.

1995 ◽  
Vol 198 (4) ◽  
pp. 975-987 ◽  
Author(s):  
A C Guimaraes ◽  
W Herzog ◽  
T L Allinger ◽  
Y T Zhang
Keyword(s):  
Soleus Muscle ◽  
Adaptive Filtering ◽  
Muscle Activation ◽  
Stance Phase ◽  
Force Production ◽  
Muscle Length ◽  
Force Transducer ◽  
Shortening Velocity ◽  
Integrated Emg ◽  
Filtering Approach

The relationship between force and electromyographic (EMG) signals of the cat soleus muscle was obtained for three animals during locomotion at five different speeds (154 steps), using implanted EMG electrodes and a force transducer. Experimentally obtained force-IEMG (= integrated EMG) relationships were compared with theoretically predicted instantaneous activation levels calculated by dividing the measured force by the predicted maximal force that the muscle could possibly generate as a function of its instantaneous contractile conditions. In addition, muscular forces were estimated from the corresponding EMG records exclusively using an adaptive filtering approach. Mean force-IEMG relationships were highly non-linear but similar in shape for different cats and different speeds of locomotion. The theoretically predicted activation-time plots typically showed two peaks, as did the IEMG-time plots. The first IEMG peak tended to be higher than the second one and it appeared to be associated with the initial priming of the muscle for force production at paw contact and the peak force observed early during the stance phase. The second IEMG peak appeared to be a burst of high muscle activation, which might have compensated for the levels of muscle length and shortening velocity that were suboptimal during the latter part of the stance phase. Although it was difficult to explain the soleus forces on the basis of the theoretically predicted instantaneous activation levels, it was straightforward to approximate these forces accurately from EMG data using an adaptive filtering approach.

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