Cross-bridge kinetics and shortening in smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1334-1337 ◽  
Author(s):  
Per Hellstrand
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Isometric Force ◽  
Muscle Mechanics ◽  
Cross Bridge ◽  
Intracellular Ca ◽  
Cross Bridges ◽  
Latch State ◽  
Smooth Muscle Mechanics ◽  
Low Rate

Stiffness measurements were performed on smooth muscle preparations from guinea-pig taenia coli to obtain information on the number of attached cross bridges under varying contractile conditions. The normalized stiffness of the cross-bridge system in smooth muscle may be of a magnitude similar to that assumed in skeletal muscle. Transition from isometric contraction to unloaded shortening was associated with a decrease in stiffness to 50% or less of the isometric value, slightly higher than that found in skeletal muscle fibers. Comparison of phasic (5 s) and tonic (5 min) contractions showed lower Vmax, intracellular [Ca2+], and myosin 20 kDa light chain phosphorylation at 5 min, indicating development of a latch state. Isometric force and stiffness were identical in the two types of contraction. However, stiffness during unloaded shortening was greater in the latch state, which may be the result of the presence of a population of cross bridges with a low rate constant for detachment.Key words: smooth muscle mechanics, cross bridges, latch, myosin phosphorylation.

An expanded latch-bridge model of protein kinase C-mediated smooth muscle contraction

2005 ◽  
Vol 98 (4) ◽  
pp. 1356-1365 ◽  
Author(s):  
Chi-Ming Hai ◽  
Hak Rim Kim
Keyword(s):  
Smooth Muscle ◽  
Atpase Activity ◽  
Thin Filament ◽  
Muscle Mechanics ◽  
Smooth Muscle Contraction ◽  
Myosin Phosphorylation ◽  
Cross Bridge ◽  
Bridge Model ◽  
Cross Bridges ◽  
Smooth Muscle Mechanics

A thin-filament-regulated latch-bridge model of smooth muscle contraction is proposed to integrate thin-filament-based inhibition of actomyosin ATPase activity with myosin phosphorylation in the regulation of smooth muscle mechanics. The model included two latch-bridge cycles, one of which was identical to the four-state model as proposed by Hai and Murphy ( Am J Physiol Cell Physiol 255: C86–C94, 1988), whereas the ultraslow cross-bridge cycle has lower cross-bridge cycling rates. The model-fitted phorbol ester induced slow contractions at constant myosin phosphorylation and predicted steeper dependence of force on myosin phosphorylation in phorbol ester-stimulated smooth muscle. By shifting cross bridges between the two latch-bridge cycles, the model predicts that a smooth muscle cell can either maintain force at extremely low-energy cost or change its contractile state rapidly, if necessary. Depending on the fraction of cross bridges engaged in the ultraslow latch-bridge cycle, the model predicted biphasic kinetics of smooth muscle mechanics and variable steady-state dependencies of force and shortening velocity on myosin phosphorylation. These results suggest that thin-filament-based regulatory proteins may function as tuners of actomyosin ATPase activity, thus allowing a smooth muscle cell to have two discrete cross-bridge cycles with different cross-bridge cycling rates.

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.

Cooperative attachment of cross bridges predicts regulation of smooth muscle force by myosin phosphorylation

2004 ◽  
Vol 287 (3) ◽  
pp. C594-C602 ◽  
Author(s):  
Christopher M. Rembold ◽  
Robert L. Wardle ◽  
Christopher J. Wingard ◽  
Timothy W. Batts ◽  
Elaine F. Etter ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Time Course ◽  
Muscle Force ◽  
Regulatory System ◽  
Force Development ◽  
Cross Bridge ◽  
Cross Bridges ◽  
The Relationship ◽  
Cooperative Activation

Serine 19 phosphorylation of the myosin regulatory light chain (MRLC) appears to be the primary determinant of smooth muscle force development. The relationship between MRLC phosphorylation and force is nonlinear, showing that phosphorylation is not a simple switch regulating the number of cycling cross bridges. We reexamined the MRLC phosphorylation-force relationship in slow, tonic swine carotid media; fast, phasic rabbit urinary bladder detrusor; and very fast, tonic rat anococcygeus. We found a sigmoidal dependence of force on MRLC phosphorylation in all three tissues with a threshold for force development of ∼0.15 mol Pi/mol MRLC. This behavior suggests that force is regulated in a highly cooperative manner. We then determined whether a model that employs both the latch-bridge hypothesis and cooperative activation could reproduce the relationship between Ser19-MRLC phosphorylation and force without the need for a second regulatory system. We based this model on skeletal muscle in which attached cross bridges cooperatively activate thin filaments to facilitate cross-bridge attachment. We found that such a model describes both the steady-state and time-course relationship between Ser19-MRLC phosphorylation and force. The model required both cooperative activation and latch-bridge formation to predict force. The best fit of the model occurred when binding of a cross bridge cooperatively activated seven myosin binding sites on the thin filament. This result suggests cooperative mechanisms analogous to skeletal muscle that will require testing.

Regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle

1988 ◽  
Vol 255 (1) ◽  
pp. C86-C94 ◽  
Author(s):  
C. M. Hai ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Shortening Velocity ◽  
Internal Load ◽  
Cross Bridge ◽  
Bridge Model ◽  
The Family ◽  
Cross Bridges ◽  
Latch State ◽  
The Relationship ◽  
State Stress

We have proposed a model that incorporates a dephosphorylated "latch bridge" to explain the mechanics and energetics of smooth muscle. Cross-bridge phosphorylation is proposed as a prerequisite for cross-bridge attachment and rapid cycling. Features of the model are 1) myosin light chain kinase and phosphatase can act on both free and attached cross bridges, 2) dephosphorylation of an attached phosphorylated cross bridge produces a noncycling "latch bridge," and 3) latch bridges have a slow detachment rate. This model quantitatively predicts the latch state: stress maintenance with reduced phosphorylation, cross-bridge cycling rates, and ATP consumption. In this study, we adapted A. F. Huxley's formulation of crossbridge cycling (A. F. Huxley, Progr. Biophys. Mol. Biol. 7: 255-318, 1957) to the latch-bridge model to predict the relationship between isotonic shortening velocity and phosphorylation. The model successfully predicted the linear dependence of maximum shortening velocity at zero external load (V0) on phosphorylation, as well as the family of stress-velocity curves determined at different times during a contraction when phosphorylation values varied. The model implies that it is unnecessary to invoke an internal load or multiple regulatory mechanisms to explain regulation of V0 in smooth muscle.

Cross-bridge phosphorylation and regulation of latch state in smooth muscle

1988 ◽  
Vol 254 (1) ◽  
pp. C99-C106 ◽  
Author(s):  
C. M. Hai ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Experimental Observation ◽  
Rate Constants ◽  
Regulatory Mechanism ◽  
Myosin Phosphorylation ◽  
Model Simulations ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Latch State

We have developed a minimum kinetic model for cross-bridge interactions with the thin filament in smooth muscle. The model hypothesizes two types of cross-bridge interactions: 1) cycling phosphorylated cross bridges and 2) noncycling dephosphorylated cross bridges ("latch bridges"). The major assumptions are that 1) Ca2+-dependent myosin phosphorylation is the only postulated regulatory mechanism, 2) each myosin head acts independently, and 3) latch bridges are formed by dephosphorylation of an attached cross bridge. Rate constants were resolved by fitting data on the time courses of myosin phosphorylation and stress development. Comparison of the rate constants indicates that latch-bridge detachment is the rate-limiting step. Model simulations predicted a hyperbolic dependence of steady-state stress on myosin phosphorylation, which corresponded with the experimental observation of high values of stress with low levels of phosphorylation in intact tissues. Model simulations also predicted the experimental observation that an initial phosphorylation transient only accelerates stress development, with no effect on the final steady-state levels of stress. Because the only Ca2+-dependent regulatory mechanism in this model was activation of myosin light chain kinase, these results are consistent with the hypothesis that myosin phosphorylation is both necessary and sufficient for the development of the latch state.

Force recovery after activated shortening in whole skeletal muscle: transient and steady-state aspects of force depression

2005 ◽  
Vol 99 (1) ◽  
pp. 252-260 ◽  
Author(s):  
David T. Corr ◽  
Walter Herzog
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Isometric Force ◽  
Mechanical Work ◽  
Transient Phenomena ◽  
Cross Bridge ◽  
Force Depression ◽  
In Situ Experiments ◽  
Force Recovery ◽  
Cross Bridges

The depression of isometric force after active shortening is a well-accepted characteristic of skeletal muscle, yet its mechanisms remain unknown. Although traditionally analyzed at steady state, transient phenomena caused, at least in part, by cross-bridge kinetics may provide novel insight into the mechanisms associated with force depression (FD). To identify the transient aspects of FD and its relation to shortening speed, shortening amplitude, and muscle mechanical work, in situ experiments were conducted in soleus muscle-tendon units of anesthetized cats. The period immediately after shortening, in which force recovers toward steady state, was fit by using an exponential recovery function ( R2 > 0.99). Statistical analyses revealed that steady-state FD (FDss) increased with shortening amplitude and mechanical work. This FDss increase was always accompanied by a significant decrease in force recovery rate. Furthermore, a significant reduction in stiffness was observed after all activated shortenings, presumably because of a reduced proportion of attached cross bridges. These results were interpreted with respect to the two most prominent proposed mechanisms of force depression: sarcomere length nonuniformity theory ( 7 , 32 ) and a stress-induced inhibition of cross-bridge binding in the newly formed actin-myosin overlap zone ( 14 , 28 ). We hypothesized that the latter could describe both steady-state and transient aspects of FD using a single scalar variable, the mechanical work done during shortening. As either excursion (overlap) or force (stress) is increased, mechanical work increases, and cross-bridge attachment would become more inhibited, as supported by this study in which an increase in mechanical work resulted in a slower recovery to a more depressed steady-state force.

Smooth muscle energetics and theories of cross-bridge regulation

1990 ◽  
Vol 258 (2) ◽  
pp. C369-C375 ◽  
Author(s):  
R. J. Paul
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Steady State ◽  
Time Course ◽  
Isometric Force ◽  
Muscle Energetics ◽  
Cross Bridge ◽  
Tension Cost ◽  
Low Tension ◽  
Smooth Muscle Energetics

The energetics of smooth muscle is characterized by low tension cost (rate of ATP utilization per isometric force/cross-section area), ranging from 100- to 500-fold less than skeletal muscle. The efficiency (ATP usage per work) of smooth muscle, although less well documented, is also somewhat (4-fold) less than skeletal muscle. Another well-known characteristic of smooth muscle is the linear relation between the steady-state of ATP utilization (JATP) and isometric force. Recently, Murphy and colleagues [C.-M. Hai and R. A. Murphy. Am. J. Physiol. 254 (Cell Physiol. 23) C99-C106, 1988] have put forth a kinetic model of cross-bridge regulation that predicts the time course of stress and myosin light chain phosphorylation (MLC-Pi). The energetics consequences of this model, in brief, are that the low tension cost is partly attributed to a slow detachment rate of the myosin cross bridge when dephosphorylated when attached to actin ("latch state"), whereas the lower efficiency is ascribed to a high rate of myosin phosphorylation-dephosphorylation inherent to a fit of data to this kinetic scheme. This latter corollary is somewhat controversial in light of current interpretations of smooth muscle energetics data. Using SCoP software (National Biomedical Simulation Resource, Duke University), we tested this model in terms of fitting existing data with respect to 1) is a high myosin-dephosphorylation adenosine triphosphatase (ATPase) necessary to fit the available data on the time course of stress and MLC-Pi?; and 2) can this model predict the observed linear relation between the steady-state rate of ATP hydrolysis (JATP) and isometric force?(ABSTRACT TRUNCATED AT 250 WORDS)

Time dependence of shortening velocity in tracheal smooth muscle

1986 ◽  
Vol 251 (3) ◽  
pp. C435-C442 ◽  
Author(s):  
N. L. Stephens ◽  
M. L. Kagan ◽  
C. S. Packer
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Shortening Velocity ◽  
Time Intervals ◽  
Activity Maximum ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Latch State ◽  
Stimulation Of

It seems fairly well established that in the early phase of smooth muscle contraction cross bridges cycle at a relatively rapid rate. Later on these are replaced by very slowly cycling cross bridges or "latch bridges," operating with high economy. We describe a method to identify the time at which the transition occurs. By abruptly applying a light afterload at varying time intervals after stimulation of a canine tracheal smooth muscle, a point in time could be identified when cross-bridge cycling slowed. This was called the transition time. Because this transition was load dependent, the study was repeated with the preload abruptly reduced to zero. This permitted analysis of data in terms of cross-bridge activity. Maximum zero load velocity (Vo) of the contractile machinery was plotted against time and yielded a biphasic curve. The descending limb of the curve was fitted by a curve of the form Vo(t) = alpha e-K1t + beta e-K2t; K1 was almost three times greater than K2. We speculate that the faster rate constant represented activity of the early rapidly cycling cross bridges, and the slower constant reflected cycling rates in the latch state. These results are consistent with the latch bridge hypothesis put forward by Dillon et al. and enable us to provide a first approximation of the relative velocities of the two types of cross bridges.

Muscle Cells of Hollow Organs

Physiology ◽  
1988 ◽  
Vol 3 (3) ◽  
pp. 124-128 ◽  
Author(s):  
RA Murphy
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Thin Filament ◽  
Regulatory System ◽  
Muscle Cells ◽  
Cross Bridge ◽  
Force Maintenance ◽  
Cross Bridges

Muscle cells in hollow organs must shorten and perform work much like skeletal muscle. However, they must also contract tonically to maintain organ dimensions against imposed loads. Vertebrate smooth muscle has a regulatory system involving Ca2+-stimulated cross-bridge phosphorylation that controls not only the number of cross bridges interacting with the thin filament but also controls their cycling rates. Regulation by phosphorylation and dephosphorylation lowers the efficiency of smooth muscle but contributes to a remarkable economy of force maintenance.

Airway smooth muscle mechanics: reduced activation and relaxation

1983 ◽  
Vol 54 (2) ◽  
pp. 345-348 ◽  
Author(s):  
U. Kromer ◽  
N. Stephens
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Time Course ◽  
Muscle Mechanics ◽  
Active Length ◽  
Time Courses ◽  
Tension Curves ◽  
Smooth Muscle Mechanics ◽  
Isometric Muscle

Reduced activation of skeletal muscle fibers at below-optimal lengths has been reported before. We studied tracheal smooth muscle (TSM) as a model of airway smooth muscle to see whether such a phenomenon existed in smooth muscle also; we found that active length-tension curves at normal and raised Ca2+ concentrations were significantly different. This indicated reduced activation of the TSM at below-optimal lengths. This reduction was in addition to that arising from the length-tension effect. We also studied the mechanics of relaxation in TSM and noted that in afterloaded isotonic tension records the time course of TSM relaxation appeared to closely follow that of the isometric contraction at all loads. In this it differed markedly from relaxation in skeletal muscle where the time courses of relaxation at different loads differed from each other and from that of the isometric muscle.

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