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.

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.

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.

Myosin phosphorylation and regulation of cross-bridge cycle in tracheal smooth muscle

1983 ◽  
Vol 244 (3) ◽  
pp. C182-C187 ◽  
Author(s):  
W. T. Gerthoffer ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Tracheal Smooth Muscle ◽  
Shortening Velocity ◽  
Active Stress ◽  
Myosin Phosphorylation ◽  
Cross Bridge ◽  
Rapid Changes ◽  
Cross Bridges ◽  
Resting Muscle ◽  
Isotonic Shortening

We have tested the hypothesis that phosphorylation of the 20,000-dalton myosin light chains (LC 20) in rabbit tracheal smooth muscle modulates cross-bridge kinetics and isotonic shortening velocity. The thin muscle [190 +/- 10 (SE) microns] allowed detection of rapid changes in carbachol-induced active stress development, LC 20 phosphorylation, and isotonic shortening velocities. Phosphorylation of the LC 20 in resting muscle was 0.12 +/- 0.04 mol Pi/mol LC 20. Carbachol (10(-5) M) increased the level of phosphorylation to 0.46 +/- 0.03 mol Pi/mol LC 20 within 30 s. Phosphorylation then declined significantly as steady-state active stress was reached. A positive correlation was always found between LC 20 phosphorylation and shortening velocity. This result supports the hypothesis that the level of myosin phosphorylation was related to the mean cross-bridge cycling rate rather than the number of cross bridges contributing to the developed stress. Dephosphorylation of LC 20 occurred at about the same rate as the decline in shortening velocity and stress upon stimulus washout.

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.

scholarly journals Effect of lithium on smooth muscle contraction and phosphorylation of myosin light chain by MLCK

2010 ◽  
pp. 919-926
Author(s):  
ZY Tang ◽  
ZN Liu ◽  
L Fu ◽  
DP Chen ◽  
QD Ai ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Atpase Activity ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Contractile Activity ◽  
Smooth Muscle Contraction ◽  
Time Dependent ◽  
Dependent Manner ◽  
Myosin Phosphorylation

The aims of our study were to investigate into the effect of lithium on smooth muscle contraction and phosphorylation of myosin light chain (MLC20) by MLCK and to find out the clue of its mechanism. Isolated rabbit duodenum smooth muscle strips were used to study the effects of lithium on their contractile activity under the condition of Krebs’ solution by means of HW400S constant temperature smooth muscle trough. Myosin and MLCK were purified from the chicken gizzard smooth muscle. Myosin phosphorylation was determined by Glycerol-PAGE, myosin Mg2+-ATPase activity was measured by Pi liberation method. Lithium (10-40 mM) inhibited the contraction in duodenum in a dose-related and time-dependent manner. Lithium could also inhibit the extent of myosin phosphorylation in a dose-related and time-dependent manner, whereas it inhibited Mg2+-ATPase activity in a dose-related manner. Lithium inhibited smooth muscle contraction by inhibition of myosin phosphorylation and Mg2+-ATPase activity.

Cross-bridge regulation by Ca2+-dependent phosphorylation in amphibian smooth muscle

2001 ◽  
Vol 281 (6) ◽  
pp. R1769-R1777 ◽  
Author(s):  
C. J. Wingard ◽  
J. M. Nowocin ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Regulatory Mechanism ◽  
Smooth Muscle Contraction ◽  
Field Stimulation ◽  
Myosin Regulatory Light Chain ◽  
Rapid Rise ◽  
Shortening Velocity ◽  
Cross Bridge ◽  
Length Relationship ◽  
Cross Bridges

A covalent regulatory mechanism involving Ca2+-dependent cross-bridge phosphorylation determines both the number of cycling cross bridges and cycling kinetics in mammalian smooth muscle. Our objective was to determine whether a similar regulatory mechanism governed smooth muscle contraction from a poikilothermic amphibian in a test of the hypothesis that myosin regulatory light chain (MRLC) phosphorylation could modulate shortening velocity. We measured MRLC phosphorylation of Rana catesbiana urinary bladder strips at 25°C in tonic contractions in response to K+ depolarization, field stimulation, or carbachol stimulation. The force-length relationship was characterized by a steep ascending limb and a shallow descending limb. There was a rapid rise in unloaded shortening velocity early in a contraction, which then fell and was maintained at low rates while high force was maintained. In support of the hypothesis, we found a positive correlation of the level of myosin phosphorylation and an estimate of tissue shortening velocity. These results suggest that MRLC phosphorylation in amphibian smooth muscle modulates both the number of attached cross bridges (force) and the cross-bridge cycling kinetics (shortening velocity) as in mammalian smooth muscle.

Modulation of arterial Na+-K+-ATPase-induced [Ca2+]i reduction and relaxation by norepinephrine, ET-1, and PMA

1999 ◽  
Vol 276 (2) ◽  
pp. H651-H657 ◽  
Author(s):  
Francisco Pérez-Vizcaíno ◽  
Angel Cogolludo ◽  
Juan Tamargo
Keyword(s):  
Enzyme Activity ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Atpase Activity ◽  
Vascular Tone ◽  
Smooth Muscle Contraction ◽  
Mesenteric Arteries ◽  
Free Solution ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

Na+-K+-ATPase plays a major role in regulating membrane potential and vascular tone. We analyzed the modulation by norepinephrine (NE), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) of Na+-K+-ATPase-induced cytoplasmic free Ca2+concentration ([Ca2+]i) reduction and relaxation in isolated endothelium-denuded piglet mesenteric arteries. KCl (0.2–8.8 mM)-induced [Ca2+]ireduction and relaxation in arteries incubated in K+-free solution were used as functional indicators of Na+-K+-ATPase activity. KCl-induced relaxations after exposure to K+-free solution were associated with a reduction in [Ca2+]i, as measured by fura 2 fluorescence. However, KCl reduced [Ca2+]ibelow resting values, whereas force was reduced to near resting values. NE, ET-1, and PMA inhibited the relaxant effects of KCl, and this effect was attenuated by the protein kinase C inhibitor staurosporine but not by the phospholipase A2inhibitor quinacrine. However, ET-1 and PMA potentiated the [Ca2+]i-reducing effect of KCl. In conclusion, ET-1, PMA, and NE are functional inhibitors of Na+-K+-ATPase activity in endothelium-denuded piglet mesenteric arteries, even when the direct effect on the enzyme activity may be stimulatory rather than inhibitory. This can be explained because ET-1, PMA, and NE induce Ca2+ sensitization for smooth muscle contraction, and therefore relaxations do not parallel the reductions in [Ca2+]iafter the activation of Na+-K+-ATPase.

scholarly journals Slowly cycling Rho kinase-dependent actomyosin cross-bridge “slippage” explains intrinsic high compliance of detrusor smooth muscle

2017 ◽  
Vol 313 (1) ◽  
pp. F126-F134 ◽  
Author(s):  
Christopher J. Neal ◽  
Jia B. Lin ◽  
Tanner Hurley ◽  
Amy S. Miner ◽  
John E. Speich ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Soft Tissues ◽  
Plastic Material ◽  
Rho Kinase ◽  
Detrusor Smooth Muscle ◽  
Display Time ◽  
Protein Activation ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Dependent Viscosity

Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as “slipping” cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.

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