The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment

1997 ◽  
Vol 273 (5) ◽  
pp. H2428-H2435 ◽  
Author(s):  
Thomas Wannenburg ◽  
Paul M. L. Janssen ◽  
Dongsheng Fan ◽  
Pieter P. De Tombe
Keyword(s):  
Cardiac Muscle ◽  
Maximum Rate ◽  
Sarcomere Length ◽  
Myosin Head ◽  
Isometric Force ◽  
Force Development ◽  
Cross Bridge ◽  
Average Slope ◽  
The Cross ◽  
Kinetics Of

We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 μm). The maximum rate of ATP consumption was 1.5 nmol ⋅ s−1 ⋅ μl fiber vol−1, which represents an estimated adenosinetriphosphatase (ATPase) rate of ∼10 s−1 per myosin head at 24°C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol ⋅ mN−1 ⋅ mm−1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.

Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

2007 ◽  
Vol 293 (1) ◽  
pp. R20-R29 ◽  
Author(s):  
István Ferenc Édes ◽  
Dániel Czuriga ◽  
Gábor Csányi ◽  
Stefan Chłopicki ◽  
Fabio A. Recchia ◽  
...  
Keyword(s):  
Sarcomere Length ◽  
Species Differences ◽  
Isometric Force ◽  
Force Production ◽  
Major Influence ◽  
Turnover Rates ◽  
Force Development ◽  
Cross Bridge ◽  
The Cross ◽  
Isometric Force Production

The increase in Ca2+ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of cross-bridge turnover kinetics. Therefore, the Ca2+ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment ( ktr) were determined at different SLs (1.9 and 2.3 μm) in isolated human, murine, and porcine permeabilized cardiomyocytes. ktr was also determined in the presence of 10 mM inorganic phosphate (Pi), which interfered with the force-generating cross-bridge transitions. The increases in Ca2+ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (ΔpCa50: ∼0.11). ktr was higher ( P < 0.05) in mice than in humans or pigs at all Ca2+ concentrations ([Ca2+]) [maximum ktr ( ktr,max) at a SL of 1.9 μm and pCa 4.75: 1.33 ± 0.11, 7.44 ± 0.15, and 1.02 ± 0.05 s−1, in humans, mice, and pigs, respectively] but ktr did not depend on SL in any species. Moreover, when the ktr values for each species were expressed relative to their respective maxima, similar Ca2+ dependencies were obtained. Ten millimolar Pi decreased force to ∼60–65% and left ΔpCa50 unaltered in all three species. Pi increased ktr,max by a factor of ∼1.6 in humans and pigs and by a factor of ∼3 in mice, independent of SL. In conclusion, species differences exert a major influence on ktr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.

Skeletal and Cardiac Muscle Contractile Activation: Tropomyosin “Rocks and Rolls”

Physiology ◽  
2001 ◽  
Vol 16 (2) ◽  
pp. 49-55 ◽  
Author(s):  
A. M. Gordon ◽  
M. Regnier ◽  
E. Homsher
Keyword(s):  
Cardiac Muscle ◽  
Thin Filament ◽  
Sarcomere Length ◽  
Force Development ◽  
Cross Bridge ◽  
Functional Differences ◽  
Filament Structure ◽  
Muscle Types ◽  
Contractile Activation ◽  
Muscle Contractile

Changes in thin filament structure induced by Ca2+ binding to troponin and subsequent strong cross-bridge binding regulate additional strong cross-bridge attachment, force development, and dependence of force on sarcomere length in skeletal and cardiac muscle. Variations in activation properties account for functional differences between these muscle types.

scholarly journals Characterization of cross-bridge elasticity and kinetics of cross-bridge cycling during force development in single smooth muscle cells.

1988 ◽  
Vol 91 (6) ◽  
pp. 761-779 ◽  
Author(s):  
D M Warshaw ◽  
D D Rees ◽  
F S Fay
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Isometric Force ◽  
Force Development ◽  
Cross Bridge ◽  
Tension Recovery ◽  
Length Changes ◽  
Cross Bridges ◽  
Initial Force ◽  
Kinetics Of

Force development in smooth muscle, as in skeletal muscle, is believed to reflect recruitment of force-generating myosin cross-bridges. However, little is known about the events underlying cross-bridge recruitment as the muscle cell approaches peak isometric force and then enters a period of tension maintenance. In the present studies on single smooth muscle cells isolated from the toad (Bufo marinus) stomach muscularis, active muscle stiffness, calculated from the force response to small sinusoidal length changes (0.5% cell length, 250 Hz), was utilized to estimate the relative number of attached cross-bridges. By comparing stiffness during initial force development to stiffness during force redevelopment immediately after a quick release imposed at peak force, we propose that the instantaneous active stiffness of the cell reflects both a linearly elastic cross-bridge element having 1.5 times the compliance of the cross-bridge in frog skeletal muscle and a series elastic component having an exponential length-force relationship. At the onset of force development, the ratio of stiffness to force was 2.5 times greater than at peak isometric force. These data suggest that, upon activation, cross-bridges attach in at least two states (i.e., low-force-producing and high-force-producing) and redistribute to a steady state distribution at peak isometric force. The possibility that the cross-bridge cycling rate was modulated with time was also investigated by analyzing the time course of tension recovery to small, rapid step length changes (0.5% cell length in 2.5 ms) imposed during initial force development, at peak force, and after 15 s of tension maintenance. The rate of tension recovery slowed continuously throughout force development following activation and slowed further as force was maintained. Our results suggest that the kinetics of force production in smooth muscle may involve a redistribution of cross-bridge populations between two attached states and that the average cycling rate of these cross-bridges becomes slower with time during contraction.

scholarly journals Acceleration of Stretch Activation in Murine Myocardium due to Phosphorylation of Myosin Regulatory Light Chain

2006 ◽  
Vol 128 (3) ◽  
pp. 261-272 ◽  
Author(s):  
Julian E. Stelzer ◽  
Jitandrakumar R. Patel ◽  
Richard L. Moss
Keyword(s):  
Light Chain ◽  
Isometric Force ◽  
Systolic Function ◽  
Muscle Length ◽  
Striated Muscles ◽  
Stretch Activation ◽  
Force Transmission ◽  
Force Development ◽  
Cross Bridge ◽  
Kinetics Of

The regulatory light chains (RLCs) of vertebrate muscle myosins bind to the neck region of the heavy chain domain and are thought to play important structural roles in force transmission between the cross-bridge head and thick filament backbone. In vertebrate striated muscles, the RLCs are reversibly phosphorylated by a specific myosin light chain kinase (MLCK), and while phosphorylation has been shown to accelerate the kinetics of force development in skeletal muscle, the effects of RLC phosphorylation in cardiac muscle are not well understood. Here, we assessed the effects of RLC phosphorylation on force, and the kinetics of force development in myocardium was isolated in the presence of 2,3-butanedione monoxime (BDM) to dephosphorylate RLC, subsequently skinned, and then treated with MLCK to phosphorylate RLC. Since RLC phosphorylation may be an important determinant of stretch activation in myocardium, we recorded the force responses of skinned myocardium to sudden stretches of 1% of muscle length both before and after treatment with MLCK. MLCK increased RLC phosphorylation, increased the Ca2+ sensitivity of isometric force, reduced the steepness of the force–pCa relationship, and increased both Ca2+-activated and Ca2+-independent force. Sudden stretch of myocardium during an otherwise isometric contraction resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed redevelopment of force, i.e., stretch activation, to levels greater than pre-stretch force. MLCK had profound effects on the stretch activation responses during maximal and submaximal activations: the amplitude and rate of force decay after stretch were significantly reduced, and the rate of delayed force recovery was accelerated and its amplitude reduced. These data show that RLC phosphorylation increases force and the rate of cross-bridge recruitment in murine myocardium, which would increase power generation in vivo and thereby enhance systolic function.

scholarly journals Length and PKA Dependence of Force Generation and Loaded Shortening in Porcine Cardiac Myocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kerry S. McDonald ◽  
Laurin M. Hanft ◽  
Timothy L. Domeier ◽  
Craig A. Emter
Keyword(s):  
Cardiac Myocytes ◽  
Sarcomere Length ◽  
Isometric Force ◽  
Bimodal Distribution ◽  
Left Ventricular ◽  
Development Rate ◽  
The Other ◽  
Force Development ◽  
Ventricular Relaxation ◽  
Two Populations

In healthy hearts, ventricular ejection is determined by three myofibrillar properties; force, force development rate, and rate of loaded shortening (i.e., power). The sarcomere length and PKA dependence of these mechanical properties were measured in porcine cardiac myocytes. Permeabilized myocytes were prepared from left ventricular free walls and myocyte preparations were calcium activated to yield ~50% maximal force after which isometric force was measured at varied sarcomere lengths. Porcine myocyte preparations exhibited two populations of length-tension relationships, one being shallower than the other. Moreover, myocytes with shallow length-tension relationships displayed steeper relationships following PKA. Sarcomere length-Ktrrelationships also were measured andKtrremained nearly constant over ~2.30 μm to ~1.90 μm and then increased at lengths below 1.90 μm. Loaded-shortening and peak-normalized power output was similar at ~2.30 μm and ~1.90 μm even during activations with the same [Ca2+], implicating a myofibrillar mechanism that sustains myocyte power at lower preloads. PKA increased myocyte power and yielded greater shortening-induced cooperative deactivation in myocytes, which likely provides a myofibrillar mechanism to assist ventricular relaxation. Overall, the bimodal distribution of myocyte length-tension relationships and the PKA-mediated changes in myocyte length-tension and power are likely important modulators of Frank-Starling relationships in mammalian hearts.

scholarly journals Phosphate binding induced force-reversal occurs via slow backward cycling of cross-bridges

2020 ◽  
Author(s):  
R Stehle
Keyword(s):  
Rate Constant ◽  
Force Generation ◽  
Phosphate Binding ◽  
Reversible Process ◽  
Cross Bridge ◽  
Force Relation ◽  
The Cross ◽  
Cross Bridges ◽  
Bridge Models ◽  
Kinetics Of

ABSTRACTThe release of inorganic phosphate (Pi) from the cross-bridge is a pivotal step in the cross-bridge ATPase cycle leading to force generation. It is well known that Pi release and the force-generating step are reversible, thus increase of [Pi] decreases isometric force by product inhibition and increases the rate constant kTR of mechanically-induced force redevelopment due to the reversible redistribution of cross-bridges among non-force-generating and force-generating states. The experiments on cardiac myofibrils from guinea pig presented here show that increasing [Pi] increases kTR almost reciprocally to force, i.e., kTR ≈ 1/force. To elucidate which cross-bridge models can explain the reciprocal kTR-force relation, simulations were performed for models varying in sequence and kinetics of 1) the Pi release-rebinding equilibrium, 2) the force-generating step and its reversal, and 3) the transitions limiting forward and backward cycling of cross-bridges between non-force-generating and force-generating states. Models consisting of fast reversible force generation before/after rapid Pi release-rebinding fail to describe the kTR–force relation observed in experiments. Models consistent with the experimental kTR-force relation have in common that Pi binding and/or force-reversal are/is intrinsically slow, i.e., either Pi binding or force-reversal or both limit backward cycling of cross-bridges from force-generating to non-force-generating states.STATEMENT OF SIGNIFICANCEPrevious mechanical studies on muscle fibers, myofibrils and myosin interacting with actin revealed that force production associated to phosphate release from myosin’s active site presents a reversible process in the cross-bridge cycle. The correlation of this reversible process to the process(es) limiting kinetics of backward cycling from force-generating to non-force-generating states remained unclear.Experimental data of cardiac myofibrils and model simulations show that the combined effects of [Pi] on force and the rate constant of force redevelopment (kTR) are inconsistent with fast reversible force generation before/after rapid Pi release-rebinding. The minimum requirement in sequential models for successfully describing the experimentally observed nearly reciprocal change of force and kTR is that either the Pi binding or the force-reversal step limit backward cycling.

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