scholarly journals Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle

2020 ◽  
Author(s):  
Yong Li ◽  
Anthony L. Hessel ◽  
Andreas Unger ◽  
David Ing ◽  
Jannik Recker ◽  
...  
Keyword(s):  
Muscle Protein ◽  
Mechanical Strain ◽  
Critical Force ◽  
Passive Force ◽  
Active Force ◽  
Force Transmission ◽  
Transmission Networks ◽  
Contracting Muscle ◽  
Myosin Filaments ◽  
Active Force Generation

AbstractThe giant muscle protein titin is a major contributor to passive force; however, its role in active force generation is unresolved. Here, we use a novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic titin to quantify how titin-based forces define myocyte ultrastructure and mechanics. We show that under mechanical strain, as titin cleavage doubles from heterozygous to homozygous TC muscles, Z-disks become increasingly out of register while passive and active forces are reduced. Interactions of elastic titin with sarcomeric actin filaments are revealed. Strikingly, when titin-cleaved muscles contract, myosin-containing A-bands become split and adjacent myosin filaments move in opposite directions while also shedding myosins. This establishes intact titin filaments as critical force-transmission networks, buffering the forces observed by myosin filaments during contraction. To perform this function, elastic titin must change stiffness or extensible length, unveiling its fundamental role as an activation-dependent spring in contracting muscle.

scholarly journals Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yong Li ◽  
Anthony L Hessel ◽  
Andreas Unger ◽  
David Ing ◽  
Jannik Recker ◽  
...  
Keyword(s):  
Muscle Protein ◽  
Mechanical Strain ◽  
Critical Force ◽  
Passive Force ◽  
Active Force ◽  
Force Transmission ◽  
Transmission Networks ◽  
Contracting Muscle ◽  
Myosin Filaments ◽  
Active Force Generation

The giant muscle protein titin is a major contributor to passive force; however, its role in active force generation is unresolved. Here, we use a novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic titin to quantify how titin-based forces define myocyte ultrastructure and mechanics. We show that under mechanical strain, as TC doubles from heterozygous to homozygous TC muscles, Z-disks become increasingly out of register while passive and active forces are reduced. Interactions of elastic titin with sarcomeric actin filaments are revealed. Strikingly, when titin-cleaved muscles contract, myosin-containing A-bands become split and adjacent myosin filaments move in opposite directions while also shedding myosins. This establishes intact titin filaments as critical force-transmission networks, buffering the forces observed by myosin filaments during contraction. To perform this function, elastic titin must change stiffness or extensible length, unveiling its fundamental role as an activation-dependent spring in contracting 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 Reports of the length dependence of fatigue are greatly exaggerated

2006 ◽  
Vol 101 (1) ◽  
pp. 23-29 ◽  
Author(s):  
M. B. MacNaughton ◽  
B. R. MacIntosh
Keyword(s):  
Muscle Length ◽  
Repetitive Stimulation ◽  
Double Pulse ◽  
Medial Gastrocnemius ◽  
Passive Force ◽  
Active Force ◽  
Rightward Shift ◽  
Length Dependence ◽  
Force Depression ◽  
In Series

Relative force depression associated with muscle fatigue is reported to be greater when assessed at short vs. long muscle lengths. This appears to be due to a rightward shift in the force-length relationship. This rightward shift may be caused by stretch of in-series structures, making sarcomere lengths shorter at any given muscle length. Submaximal force-length relationships (twitch, double pulse, 50 Hz) were evaluated before and after repetitive contractions (50 Hz, 300 ms, 1/s) in an in situ preparation of the rat medial gastrocnemius muscle. In some experiments, fascicle lengths were measured with sonomicrometry. Before repetitive stimulation, fascicle lengths were 11.3 ± 0.8, 12.8 ± 0.9, and 14.4 ± 1.2 mm at lengths corresponding to −3.6, 0, and 3.6 mm where 0 is a reference length that corresponds with maximal active force for double-pulse stimulation. After repetitive stimulation, there was no change in fascicle lengths; these lengths were 11.4 ± 0.8, 12.6 ± 0.9, and 14.2 ± 1.2 mm. The length dependence of fatigue was, therefore, not due to a stretch of in-series structures. Interestingly, the rightward shift that was evident when active force was calculated in the traditional way (subtraction of the passive force measured before contraction) was not seen when active force was calculated by subtracting the passive force that was associated with the fascicle length reached at the peak of the contraction. This calculation is based on the assumption that passive force decreases as the fascicles shorten during a fixed-end contraction. This alternative calculation revealed similar postfatigue absolute active force depression at all lengths. In relative terms, a length dependence of fatigue was still evident, but this was greatly diminished compared with that observed when active force was calculated with the traditional method.

Tilting of the light-chain region of myosin during step length changes and active force generation in skeletal muscle

Nature ◽  
1995 ◽  
Vol 375 (6533) ◽  
pp. 688-691 ◽  
Author(s):  
Malcolm Irving ◽  
Taylor St Claire Alien ◽  
Cibele Sabido-David ◽  
James S. Craik ◽  
Birgit Brandmeier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Light Chain ◽  
Step Length ◽  
Force Generation ◽  
Active Force ◽  
Length Changes ◽  
Active Force Generation

scholarly journals Role of desmin in active force transmission and maintenance of structure during growth of urinary bladder

2008 ◽  
Vol 295 (2) ◽  
pp. C324-C331 ◽  
Author(s):  
R. Sjuve Scott ◽  
Z. Li ◽  
D. Paulin ◽  
B. Uvelius ◽  
J. V. Small ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Structural Changes ◽  
Wall Structure ◽  
Intermediate Filament Protein ◽  
Active Force ◽  
Force Transmission ◽  
Bladder Smooth Muscle ◽  
Shortening Velocity

Role of the intermediate filament protein desmin in hypertrophy of smooth muscle was examined in desmin-deficient mice (Des−/−). A partial obstruction of the urethra was created, and after 9–19 days bladder weight increased approximately threefold in both Des−/− and wild type (Des+/+) animals. Bladder growth was associated with the synthesis of actin and myosin. In the hypertrophic Des+/+ bladder, the relative content of desmin increased. In Des−/−mice, desmin was absent. No alterations in the amount of vimentin were observed. Although Des−/− obstructed bladders were capable of growth, they had structural changes with a partial disruption of the wall. Des−/−bladders had slightly lower passive stress and significantly lower active stress compared with Des+/+. Des−/−preparations had lower shortening velocity. During hypertrophy, these structural and mechanical alterations in the Des−/−urinary bladder became more pronounced. In conclusion, desmin in the bladder smooth muscle is not needed for growth but has a role in active force transmission and maintenance of wall structure.

scholarly journals Troponin and Titin Coordinately Regulate Length-dependent Activation in Skinned Porcine Ventricular Muscle

2008 ◽  
Vol 131 (3) ◽  
pp. 275-283 ◽  
Author(s):  
Takako Terui ◽  
Munguntsetseg Sodnomtseren ◽  
Douchi Matsuba ◽  
Jun Udaka ◽  
Shin'ichi Ishiwata ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Left Ventricular ◽  
Ventricular Muscle ◽  
Passive Force ◽  
Active Force ◽  
Fast Skeletal Muscle ◽  
Thin Filaments ◽  
Cross Bridges ◽  
Length Dependent Activation

We investigated the molecular mechanism by which troponin (Tn) regulates the Frank-Starling mechanism of the heart. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal Tn (sTn) attenuated length-dependent activation in skinned porcine left ventricular muscle, to a magnitude similar to that observed in rabbit fast skeletal muscle. The rate of force redevelopment increased upon sTn reconstitution at submaximal levels, coupled with an increase in Ca2+ sensitivity of force, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force. An increase in titin-based passive force, induced by manipulating the prehistory of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca2+ sensitivity of force. These findings demonstrate that Tn plays an important role in the Frank-Starling mechanism of the heart via on–off switching of the thin filament state, in concert with titin-based regulation.

Outer hair cell active force generation in the cochlear environment

2007 ◽  
Vol 122 (4) ◽  
pp. 2215-2225 ◽  
Author(s):  
Zhijie Liao ◽  
Shengran Feng ◽  
Aleksander S. Popel ◽  
William E. Brownell ◽  
Alexander A. Spector
Keyword(s):  
Hair Cell ◽  
Outer Hair Cell ◽  
Force Generation ◽  
Active Force ◽  
Active Force Generation
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