Stimulation rate, potentiators, and sarcomere length-tension relationship of muscle

1985 ◽  
Vol 249 (5) ◽  
pp. C497-C502 ◽  
Author(s):  
L. C. Rome ◽  
D. L. Morgan ◽  
F. J. Julian
Keyword(s):  
Thin Filament ◽  
Sarcomere Length ◽  
Rana Temporaria ◽  
Maximal Level ◽  
Stimulation Rate ◽  
Mechanical Interference ◽  
Tension Generation ◽  
Cross Bridges ◽  
Relationship Of ◽  
Length Dependent Activation

Isometric tetani of single muscle fibers of Rana temporaria were studied as a function of stimulation rate, sarcomere length (1.7-2.3 micron), twitch-to-tetanus ratio, and exposure to twitch potentiators (Zn2+ and NO3-) at 20 degrees C. As the stimulation rate was decreased below a maximal level, tension generation decreased. This depression in tension generation was more pronounced at shorter sarcomere lengths. Therefore the magnitude and shape of the sarcomere length curve was dependent on stimulation rate. Although the depression in tension generation was always accompanied by a noticeable ripple in the tension record in fibers with large twitch-to-tetanus ratios, it could be observed even during well-fused tetani in fibers with low twitch-to-tetanus ratios. In all fibers, however, high stimulation rates or exposure to potentiators resulted in maximum tension generation at each length, and the sarcomere length-tension curve followed that found by Gordon, Huxley, and Julian. This indicates that the fall in tension between sarcomere lengths of 2.0 and 1.7 micron is not due to length-dependent activation but is more likely to be the result of mechanical interference in the force-generating interaction between cross bridges and thin filament sites.

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.

scholarly journals Effects of ramp shortening during linear phase of relaxation on [Ca2+]i in intact skeletal muscle fibers

1999 ◽  
Vol 276 (1) ◽  
pp. C152-C160 ◽  
Author(s):  
Yandong Jiang ◽  
Fred J. Julian
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Sarcomere Length ◽  
Muscle Fibers ◽  
Linear Phase ◽  
Fixed Size ◽  
Skeletal Muscle Fibers ◽  
Straight Line ◽  
Sigmoidal Curve ◽  
Cross Bridges

The effects of shortening distance at V u, the unloaded shortening speed, and filament overlap on the amount of extra Ca2+ released during relaxation in muscle, as indicated by the bump area, were studied. Single, intact frog skeletal muscle fibers at 3°C were used. The myoplasmic free Ca2+ concentration ([Ca2+]i) was estimated by using fura 2 salt injected into the myoplasm. Ramps were applied, either at full overlap with different sizes or at varying overlaps with a fixed size, in the linear phase of relaxation. At full overlap, a plot of bump area vs. ramp size was fit by using a sigmoidal curve with one-half of the bump area equal to 25.9 nm. With a fixed ramp size of 100 nm/half-sarcomere, the plot of bump area vs. mean sarcomere length (SLm) was fit by a straight line intersecting the SLm axis at ∼3.5 μm, close to just no overlap. The results suggest that the transition in the distribution of attached cross bridges from the isometric case to one appropriate for unloaded shortening at V u is completed within 50 nm/half-sarcomere and support the view that attached cross bridges in the overlap zone influence the affinity of Ca2+for troponin C in the thin filament.

Myofilament lattice spacing as a function of sarcomere length in isolated rat myocardium

2000 ◽  
Vol 279 (5) ◽  
pp. H2568-H2573 ◽  
Author(s):  
Thomas C. Irving ◽  
John Konhilas ◽  
Darold Perry ◽  
Robert Fischetti ◽  
Pieter P. de Tombe
Keyword(s):  
Lattice Spacing ◽  
Sarcomere Length ◽  
Calcium Sensitivity ◽  
Model Systems ◽  
X Ray Diffraction ◽  
Skinned Muscle ◽  
Intact Muscle ◽  
Myosin Interaction ◽  
Relationship Of ◽  
Length Dependent Activation

The Frank-Starling relationship of the heart has, as its molecular basis, an increase in the activation of myofibrils by calcium as the sarcomere length increases. It has been suggested that this phenomenon may be due to myofilaments moving closer together at longer lengths, thereby enhancing the probability of favorable acto-myosin interaction, resulting in increased calcium sensitivity. Accordingly, we have developed an apparatus so as to obtain accurate measurements of myocardial interfilament spacing (by synchrotron X-ray diffraction) as a function of sarcomere length (by video microscopy) over the working range of the heart, using skinned as well as intact rat trabeculas as model systems. In both these systems, lattice spacing decreased significantly as sarcomere length was increased. Furthermore, lattice spacing in the intact muscle was significantly smaller than that in the skinned muscle at all sarcomere lengths studied. These observations are consistent with the hypothesis that lattice spacing underlies length-dependent activation in the myocardium.

scholarly journals Developmental increase in β-MHC enhances sarcomere length–dependent activation in the myocardium

2019 ◽  
Vol 151 (5) ◽  
pp. 635-644 ◽  
Author(s):  
Sherif M. Reda ◽  
Sampath K. Gollapudi ◽  
Murali Chandra
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Sarcomere Length ◽  
Contractile Function ◽  
Thin Filaments ◽  
Cooperative Effects ◽  
Mediated Effects ◽  
Contractile Parameters ◽  
Cross Bridges ◽  
Length Dependent Activation

Shifts in myosin heavy chain (MHC) isoforms in cardiac myocytes have been shown to alter cardiac muscle function not only in healthy developing hearts but also in diseased hearts. In guinea pig hearts, there is a large age-dependent shift in MHC isoforms from 80% α-MHC/20% β-MHC at 3 wk to 14% α-MHC/86% β-MHC at 11 wk. Because kinetic differences in α- and β-MHC cross-bridges (XBs) are known to impart different cooperative effects on thin filaments, we hypothesize here that differences in α- and β-MHC expression in guinea pig cardiac muscle impact sarcomere length (SL)–dependent contractile function. We therefore measure steady state and dynamic contractile parameters in detergent-skinned cardiac muscle preparations isolated from the left ventricles of young (3 wk old) or adult (11 wk old) guinea pigs at two different SLs: short (1.9 µm) and long (2.3 µm). Our data show that SL-dependent effects on contractile parameters are augmented in adult guinea pig cardiac muscle preparations. Notably, the SL-mediated increase in myofilament Ca2+ sensitivity (ΔpCa50) is twofold greater in adult guinea pig muscle preparations (ΔpCa50 being 0.11 units in adult preparations but only 0.05 units in young preparations). Furthermore, adult guinea pig cardiac muscle preparations display greater SL-dependent changes than young muscle preparations in (1) the magnitude of length-mediated increase in the recruitment of new force-bearing XBs, (2) XB detachment rate, (3) XB strain-mediated effects on other force-bearing XBs, and (4) the rate constant of force redevelopment. Our findings suggest that increased β-MHC expression enhances length-dependent activation in the adult guinea pig cardiac myocardium.

scholarly journals Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses

1999 ◽  
Vol 276 (5) ◽  
pp. H1734-H1754 ◽  
Author(s):  
J. Jeremy Rice ◽  
Raimond L. Winslow ◽  
William C. Hunter
Keyword(s):  
Steady State ◽  
Thin Filament ◽  
Sarcomere Length ◽  
Isometric Force ◽  
Muscle Length ◽  
Dynamic Responses ◽  
Force Generation ◽  
Cross Bridge ◽  
Multiple Cross ◽  
Cross Bridges

Length-dependent steady-state and dynamic responses of five models of isometric force generation in cardiac myofilaments were compared with similar experimental data from the literature. The models were constructed by assuming different subsets of three putative cooperative mechanisms. Cooperative mechanism 1 holds that cross-bridge binding increases the affinity of troponin for Ca2+. In the models, cooperative mechanism 1can produce steep force-Ca2+(F-Ca) relations, but apparent cooperativity is highest at midlevel Ca2+ concentrations. During twitches, cooperative mechanism 1 has the effect of increasing latency to peak as the magnitude of force increases, an effect not seen experimentally. Cooperative mechanism 2 holds that the binding of a cross bridge increases the rate of formation of neighboring cross bridges and that multiple cross bridges can maintain activation of the thin filament in the absence of Ca2+. Only cooperative mechanism 2 can produce sarcomere length (SL)-dependent prolongation of twitches, but this mechanism has little effect on steady-state F-Ca relations. Cooperativity mechanism 3 is designed to simulate end-to-end interactions between adjacent troponin and tropomyosin. This mechanism can produce steep F-Ca relations with appropriate SL-dependent changes in Ca2+ sensitivity. With the assumption that tropomyosin shifting is faster than cross-bridge cycling, cooperative mechanism 3produces twitches where latency to peak is independent of the magnitude of force, as seen experimentally.

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 Engineered Thin Filament Mutations to Study the Sarcomere Length Dependence of Cardiac Muscle Contractility

2018 ◽  
Vol 114 (3) ◽  
pp. 313a-314a
Author(s):  
Joseph D. Powers ◽  
Farid Moussavi-Harami ◽  
Jil C. Tardiff ◽  
Jennifer Davis ◽  
Michael Regnier
Keyword(s):  
Cardiac Muscle ◽  
Thin Filament ◽  
Sarcomere Length ◽  
Muscle Contractility ◽  
Length Dependence

Functional and evolutionary relationships of troponin C

2007 ◽  
Vol 32 (1) ◽  
pp. 16-27 ◽  
Author(s):  
Todd E. Gillis ◽  
Christian R. Marshall ◽  
Glen F. Tibbits
Keyword(s):  
Functional Properties ◽  
Thin Filament ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Extensive Study ◽  
Troponin C ◽  
High Conservation ◽  
Cross Bridges ◽  
And Function

Striated muscle contraction is initiated when, following membrane depolarization, Ca2+ binds to the low-affinity Ca2+ binding sites of troponin C (TnC). The Ca2+ activation of this protein results in a rearrangement of the components (troponin I, troponin T, and tropomyosin) of the thin filament, resulting in increased interaction between actin and myosin and the formation of cross bridges. The functional properties of this protein are therefore critical in determining the active properties of striated muscle. To date there are 61 known TnCs that have been cloned from 41 vertebrate and invertebrate species. In vertebrate species there are also distinct fast skeletal muscle and cardiac TnC proteins. While there is relatively high conservation of the amino acid sequence of TnC homologs between species and tissue types, there is wide variation in the functional properties of these proteins. To date there has been extensive study of the structure and function of this protein and how differences in these translate into the functional properties of muscles. The purpose of this work is to integrate these studies of TnC with phylogenetic analysis to investigate how changes in the sequence and function of this protein, integrate with the evolution of striated muscle.

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