Calcium, Cross-Bridges, and the Frank-Starling Relationship

Physiology ◽  
2001 ◽  
Vol 16 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Franklin Fuchs ◽  
Stephen H. Smith
Keyword(s):  
Cardiac Muscle ◽  
Thin Filament ◽  
Muscle Length ◽  
Active Force ◽  
Length Dependence ◽  
Myosin Filaments ◽  
Cross Bridges

The steep relationship between active force and length in cardiac muscle is based on a length dependence of myofilament Ca2+ sensitivity. However, it is not muscle length but the lateral spacing between actin and myosin filaments that sets the level of Ca2+ sensitivity, mainly through modulation of myosin-mediated activation of the thin filament.

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.

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

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.

Length vs. active force relationship in single isolated smooth muscle cells

1991 ◽  
Vol 260 (5) ◽  
pp. C1104-C1112 ◽  
Author(s):  
D. E. Harris ◽  
D. M. Warshaw
Keyword(s):  
Smooth Muscle ◽  
Elastic Modulus ◽  
Smooth Muscle Cells ◽  
Force Measurement ◽  
Muscle Length ◽  
Muscle Cells ◽  
Active Force ◽  
Length Changes ◽  
Cross Bridges ◽  
Force Relationship

The length vs. active force relationship (L-F) may provide information about changes in smooth muscle contractile protein interactions as muscle length changes. To characterize the L-F in single toad stomach smooth muscle cells, cells were attached to a force measurement system, electrically stimulated, and isometric force and elastic modulus (an estimate of the number of attached cross bridges) determined at different cell lengths. Cells generated maximum stress (Pmax = 152.5 mN/mm2) and elastic modulus (Eact = 0.68 x 10(4) mN/mm2) at their rest length (Lcell = 78.0 microns; distance between cell attachments). At shorter lengths, active force and elastic modulus declined proportionally with active force eliminated at 0.4 Lcell. Stretching the relaxed cells up to 1.4 Lcell shifted the subsequent L-F along the length axis by the amount of the stretch but did not change Pmax or the shape of the L-F. In activated cells, force was a function of cell length rather than of shortening history. We interpret these findings as evidence that 1) Lcell is close to the optimum length for force generation, 2) the decline in force at lengths less than Lcell results from a reduced number of attached cross bridges, and 3) stretching relaxed smooth muscle cells may not move the contractile units to new positions on their L-F.

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.

Effect of length and cross-bridge attachment on Ca2+ binding to cardiac troponin C

1987 ◽  
Vol 253 (1) ◽  
pp. C90-C96 ◽  
Author(s):  
P. A. Hofmann ◽  
F. Fuchs
Keyword(s):  
Cardiac Muscle ◽  
Cardiac Troponin ◽  
Sarcomere Length ◽  
Troponin C ◽  
Saturation Curve ◽  
Cross Bridge ◽  
Cardiac Troponin C ◽  
Length Dependence ◽  
Length Relationship ◽  
Cross Bridges

The sensitivity of skinned cardiac muscle bundles to Ca2+ is a function of sarcomere length. Ca2+ sensitivity is increased as fiber length is extended along the ascending limb of the force-length curve and it has been suggested that this phenomenon makes a major contribution to the steep force-length relationship that exists in living cardiac muscle. To gain greater insight into the mechanism behind the length dependence of Ca2+ sensitivity isotopic measurements of Ca2+ binding to detergent-extracted bovine, ventricular muscle bundles were made under conditions in which troponin C was the only major Ca2+ binding species. Experiments were designed to determine whether 1) Ca2+-troponin C affinity varies in the sarcomere length range corresponding to the ascending limb of the force-length curve, and 2) Ca2+ binding correlates with length per se or with changes in the number of length-dependent cross-bridge attachments. Measurements were made of Ca2+ binding in the rigor and relaxed states. The latter state was produced by suppressing actin-myosin interaction with the phosphate analogue, sodium vanadate. After vanadate treatment it is possible to obtain a complete Ca2+ saturation curve in the presence of physiological MgATP concentrations and at constant sarcomere length. The results show that the binding of Ca2+ to the regulatory site of cardiac troponin C is length dependent but this length dependence is actually a dependence on the number of attached cross bridges.

Morphological Basis of the Disparity Between Muscle Length and Sarcomere Length in the Myocardium

1973 ◽  
Vol 31 ◽  
pp. 422-423
Author(s):  
G.E. Adomian ◽  
L. Chuck ◽  
W.W. Pannley
Keyword(s):  
Cardiac Muscle ◽  
Sarcomere Length ◽  
Muscle Length ◽  
Contractile Force ◽  
Direct Function ◽  
Morphological Basis ◽  
Tension Curve

Sonnenblick, et al, have shown that sarcomeres change length as a function of cardiac muscle length along the ascending portion of the length-tension curve. This allows the contractile force to be expressed as a direct function of sarcomere length. Below L max, muscle length is directly related to sarcomere length at lengths greater than 85% of optimum. However, beyond the apex of the tension-length curve, i.e. L max, a disparity occurs between cardiac muscle length and sarcomere length. To account for this disproportionate increase in muscle length as sarcomere length remains relatively stable, the concept of fiber slippage was suggested as a plausible explanation. These observations have subsequently been extended to the intact ventricle.

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
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