scholarly journals The effect of altered temperature on Ca2(+)-sensitive force in permeabilized myocardium and skeletal muscle. Evidence for force dependence of thin filament activation.

1990 ◽  
Vol 96 (6) ◽  
pp. 1221-1245 ◽  
Author(s):  
N K Sweitzer ◽  
R L Moss
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Thin Filament ◽  
Calcium Sensitivity ◽  
Differential Sensitivity ◽  
Fiber Types ◽  
Tension Development ◽  
Maximum Tension ◽  
Filament Activation ◽  
Muscle Types

The effect of changes in temperature on the calcium sensitivity of tension development was examined in permeabilized cellular preparations of rat ventricle and rabbit psoas muscle. Maximum force and Ca2+ sensitivity of force development increased with temperature in both muscle types. Cardiac muscle was more sensitive to changes in temperature than skeletal muscle in the range 10-15 degrees C. It was postulated that the level of thin filament activation may be decreased by cooling. To investigate this possibility, troponin C (TnC) was partially extracted from both muscle types, thus decreasing the level of thin filament activation independent of temperature and, at least in skeletal muscle fibers, decreasing cooperative activation of the thin filament as well. TnC extraction from cardiac muscle reduced the calcium sensitivity of tension less than did extraction of TnC from skeletal muscle. In skeletal muscle the midpoint shift of the tension-pCa curve with altered temperature was greater after TnC extraction than in control fibers. Calcium sensitivity of tension development was proportional to the maximum tension generated in cardiac or skeletal muscle under all conditions studied. Based on these results, we conclude that (a) maximum tension-generating capability and calcium sensitivity of tension development are related, perhaps causally, in fast skeletal and cardiac muscles, and (b) thin filament activation is less cooperative in cardiac muscle than in skeletal muscle, which explains the differential sensitivity of the two fiber types to temperature and TnC extraction. Reducing thin filament cooperativity in skeletal muscle by TnC extraction results in a response to temperature similar to that of control cardiac cells. This study provides evidence that force levels in striated muscle influence the calcium binding affinity of TnC.

scholarly journals Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges

2012 ◽  
Vol 303 (7) ◽  
pp. H863-H870 ◽  
Author(s):  
F. Steven Korte ◽  
Erik R. Feest ◽  
Maria V. Razumova ◽  
An-Yue Tu ◽  
Michael Regnier
Keyword(s):  
Cardiac Muscle ◽  
Cardiac Troponin ◽  
Thin Filament ◽  
Sarcomere Length ◽  
Calcium Sensitivity ◽  
Cardiac Troponin C ◽  
Filament Activation ◽  
Osmotic Compression ◽  
Butanedione Monoxime ◽  
Contractile Activation

Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere length (SL) in cardiac muscle and is considered to be the cellular basis of the Frank-Starling law of the heart. SL dependence may involve changes in myofilament lattice spacing and/or myosin crossbridge orientation to increase probability of binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC) variant, which has enhanced Ca2+ binding affinity, to test the hypotheses that the intrinsic properties of cTnC are important in determining 1) thin filament binding site availability and responsiveness to crossbridge activation and 2) SL dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost SL dependence of the Ca2+ sensitivity of force. This occurred despite maintaining the typical SL-dependent changes in maximal force (Fmax). Osmotic compression of preparations at SL 2.0 μm with 3% dextran increased Fmax but not pCa50 in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC-cTn exchanged trabeculae exhibited increases in both Fmax and pCa50. Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 μm decreased Fmax and pCa50 in WT cTnC-cTn trabeculae to levels measured at SL 2.0 μm, whereas only Fmax was decreased with L48Q cTnC-cTn. Overall, these results suggest that L48Q cTnC confers reduced crossbridge dependence of thin filament activation in cardiac muscle and that changes in the Ca2+ sensitivity of force in response to changes in SL are at least partially dependent on properties of thin filament troponin.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

scholarly journals Contributions of Ca 2+ -Independent Thin Filament Activation to Cardiac Muscle Function

2015 ◽  
Vol 109 (10) ◽  
pp. 2101-2112 ◽  
Author(s):  
Yasser Aboelkassem ◽  
Jordan A. Bonilla ◽  
Kimberly J. McCabe ◽  
Stuart G. Campbell
Keyword(s):  
Cardiac Muscle ◽  
Muscle Function ◽  
Thin Filament ◽  
Filament Activation

Abstract 226: Elucidating the Mechanism of Reduced Length-dependent Activation Due to a Dilated Cardiomyopathy-associated Mutation in Tropomyosin

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Joseph D Powers ◽  
Farid Moussavi-Harami ◽  
Maria Razumova ◽  
Jil Tardiff ◽  
Michael Regnier
Keyword(s):  
Dilated Cardiomyopathy ◽  
Thin Filament ◽  
Calcium Sensitivity ◽  
Experimental Chamber ◽  
Binding Inhibition ◽  
Intact Muscle ◽  
Filament Activation ◽  
State Force ◽  
Length Dependent Activation ◽  
Subcellular Level

At the subcellular level, the Frank-Starling law of the heart is described by an increase in calcium sensitivity and force with increased sarcomere length (SL). We examine how this relationship is affected by a dilated cardiomyopathy-associated mutation in tropomyosin (D230N, denoted Tm D230N ) by measuring contractility of intact and permeabilized cardiac muscle preparations at short (2.0 μm) and long (2.3 μm) SL. Transgenic mouse hearts containing the Tm D230N mutation have significantly dilated hearts and reduced cardiac output by ~6 months of age. Intact trabeculae were electrically stimulated and paced at 1 Hz with oxygenated solution (30°C) circulating through the experimental chamber, and permeabilized preparations were bathed in solutions (15°C) of progressively increased [Ca 2+ ] for measures of steady-state force. For intact muscle we found that the Tm D230N mutation results in significantly reduced twitch forces at SL 2.0 and 2.3 μm relative to wild-type (WT). Also, WT trabeculae displayed a significant increase in twitch force upon increase in SL (as expected) but Tm D230N trabeculae did not, demonstrating a loss of SL dependence of contraction. In permeabilized preparations, maximal activation (pCa 4.5) of both WT and Tm D230N preparations exhibited significant SL-dependent increases in force. However, at submaximal Ca 2+ (pCa 5.8), where the heart operates, WT preparations had significant increases in force with increasing length (comparing SL 2.0 to 2.3 μm), while this length-dependence of force augmentation in Tm D230N was absent. The increase in pCa 50 (pCa that produces half-maximal force) going from SL 2.0 to 2.3 μm was significantly less for Tm D230N preparations compared to WT, owing to a significantly smaller increase in pCa 50 at SL 2.3 μm (the pCa 50 at SL 2.0 μm was not significantly different between WT and Tm D230N ). These results suggest that the Tm D230N mutation limits an increase in the Ca 2+ sensitivity of contraction as the muscle lengthens by damping thin filament activation. To further examine length-dependent effects of the Tm D230N mutation, future experiments will test conditions that augment cross-bridge binding/inhibition, and other models of dilated cardiomyopathy that inhibit thin filament activation. Funding: HL111197

scholarly journals The Role of Thin Filament Calcium Sensitivity in Modulating Relaxation Time of Soleus and EDL Skeletal Muscle

2020 ◽  
Vol 118 (3) ◽  
pp. 122a
Author(s):  
Connor Tyree ◽  
Kyra Peczkowski ◽  
Paul M. Janssen ◽  
Jill Rafael-Fortney ◽  
Jonathan P. Davis
Keyword(s):  
Skeletal Muscle ◽  
Relaxation Time ◽  
Thin Filament ◽  
Calcium Sensitivity

Selected Contribution: Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles

2000 ◽  
Vol 89 (1) ◽  
pp. 398-405 ◽  
Author(s):  
Matthew R. McCurdy ◽  
Patrick N. Colleran ◽  
Judy Muller-Delp ◽  
Michael D. Delp
Keyword(s):  
Skeletal Muscle ◽  
Orthostatic Hypotension ◽  
Sodium Nitroprusside ◽  
Hindlimb Unloading ◽  
Fiber Types ◽  
First Order ◽  
Muscle Types ◽  
Gastrocnemius Muscles ◽  
White Gastrocnemius

It has been hypothesized that microgravity-induced orthostatic hypotension may result from an exaggerated vasodilatory responsiveness of arteries. The purpose of this study was to determine whether skeletal muscle arterioles exhibit enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order arterioles isolated from soleus and white gastrocnemius muscles were tested in vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but diminished maximal vasodilation to Ado and SNP in both muscles. In addition, vasodilatory responses in arterioles from control rats varied between muscle types. Maximal dilations induced by Iso (soleus: 42 ± 6%; white gastrocnemius: 60 ± 7%) and Ado (soleus: 51 ± 8%; white gastrocnemius: 81 ± 6%) were greater in arterioles from white gastrocnemius muscles. These data do not support the hypothesis that microgravity-induced orthostatic hypotension results from an enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore, the data support the concept that dilatory responsiveness of arterioles varies in muscle composed of different fiber types.

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