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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A persistent problem with the rotating cross-bridge model for muscle contraction has been the inability to detect any large conformational changes within the myosin molecule to account for a working stroke of 5-10 nm. The recent crystal structure of myosin subfragment-1 suggests a solution to this problem by showing the presence of two distinct domains: a catalytic or motor domain, from which extends a long, 8.5-nm alpha-helix that is stabilized by the regulatory and essential light chains. Rayment et al. (1993) proposed that closure of a cleft in the motor domain could rotate the light chain-binding domain by a sufficient distance to account for the power stroke. With the development of new in vitro motility assays, and the ability to prepare unusual myosins by biochemical and molecular biological methods, we can now examine this hypothesis and explore the role of the light chains in generating force and movement. Here we will review some of these recent data and outline a possible mechanism for how light chains regulate contractile properties.
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PMID:Role of skeletal and smooth muscle myosin light chains. 778 54

Changes in the x-ray diffraction patterns produced by 100-microseconds-length steps imposed during tetanic stimulation were recorded from single intact fibers of frog tibialis anterior muscle. For shortening steps, a staircase length change was applied, with a 20-ms interval between steps. For stretches, each 20-ms cycle started with a stretch, followed after 4 ms by shortening to the original length. Each shortening step in the staircase and each stretch in the stretch/shortening protocol produced a response similar to that of a single step from the isometric steady state. The intensity of the 14.5-nm x-ray reflection arising from the axial repeat of the myosin heads along their filaments decreased after both shortening and stretch; this decrease was not accompanied by broadening along or across the meridian. The relationship between the intensity after the length step and step amplitude was approximately linear for both stretches and shortening steps, extrapolating to zero intensity for 11-nm stretches and 13-nm shortening steps, but there was no significant intensity change for the first approximately 2 nm of shortening. These results are broadly consistent with conventional models of muscle contraction in which myosin heads move through about 10 nm during the working stroke in the shortening direction, but an additional distortion of the myosin heads may be produced by a stretch.
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PMID:Changes in the x-ray diffraction pattern from single, intact muscle fibers produced by rapid shortening and stretch. 778 15

We have determined the orientation and dynamics of the putative pre-power stroke crossbridges in skinned muscle fibers labeled with maleimide spin-label at Cys-707 of myosin. Orientation was measured using electron paramagnetic resonance (EPR) and mobility by saturation transfer EPR. The crossbridges are trapped in the pre-power stroke conformation in the presence of aluminum fluoride, Ca, and ATP. In agreement with data published for unlabeled fibers (Chase et al., 1994), spin-labeled muscle fibers display 42.5% of rigor stiffness, without the generation of force. The trapped crossbridges are as disordered as the relaxed heads, but their microsecond dynamics are significantly restricted. Modeling of the immobile fraction (35%), in terms of attached heads as estimated from stiffness, suggests that the bound heads rotate with a correlation time tau r = 150-400 microseconds, as compared to tau r = 3 microseconds for the heads in relaxed fibers. These "strongly" attached myosin heads, at orientations other than in rigor, are a candidate for the state from which head rotation generates force, as postulated by H. E. Huxley (1969). Ordering of the heads may well be the structural event driving the generation of force.
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PMID:Orientation and dynamics of myosin heads in aluminum fluoride induced pre-power stroke states: an EPR study. 791 18

The decline of maximal cardiac output (Qmax) is a major factor responsible for the lower maximal oxygen consumption of elderly mammals. The lower Qmax is associated with aging-related decreases in maximal heart rate (HR-max) and maximal stroke volume (SVmax). The mechanism(s) for the slower HRmax, unchanged by exercise training, is unknown. The decrement in SVmax, however, can be improved, as shown by the enhanced systolic and diastolic properties of the elderly heart after exercise training. One major problem is diastolic dysfunction observed in the absence of disease. Diastolic dysfunction (a decrease in peak ventricular filling after systole or a prolonged relaxation of contracted muscle) results from in part a downregulation of the sarcoplasmic reticulum's (SR) calcium ATPase that sequesters cytosolic calcium via the hydrolysis of ATP. Exercise training of sedentary old mammals produces a faster relaxation and an upregulation of the SR calcium ATPase. Yet the characteristic shift of myosin toward the slower isoform is unaltered by exercise training. The molecular signals and mechanisms underlying these aging-related alterations in sedentary and physically active individuals are unknown. An enhancement of cardiac function by exercise training, though, is preserved in advanced age.
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PMID:Mechanisms for the responses of cardiac muscle to physical activity in old age. 800 3

Movement of single myosin filaments, synthesized by copolymerization of intact myosin and fluorescently labeled light meromyosin, were observed along a single actin filament suspended in solution by a dual laser trap in a fluorescence microscope. The sliding velocity of the myosin filaments was 11.0 +/- 0.2 micron/s at 27 degrees C. This is similar to that of actin moving toward the center from the tip (the physiological direction) of myosin filaments bound to a glass surface but several times larger than that in the opposite direction (Ishijima and Yanagida, 1991; Yanagida, 1993). This indicates that the movement of myosin filaments is dominated by the myosin heads on one side of the myosin filament, which are correctly oriented relative to the actin filament. The incorrectly oriented myosin heads on the other side do not interfere with the fast movement. The step size (displacement produced during one ATPase cycle) of correctly oriented myosin was estimated from the minimum number of myosin heads necessary to produce the maximum velocity. This was determined by measuring the velocities of various lengths of myosin filaments. The minimum length of the myosin filaments moving near the maximum velocity was 0.30-0.40 microns, which contains 20 +/- 5 correctly oriented myosin heads. This number leads to a myosin step size of 71 +/- 22 nm. This value probably represents the lower limit, because all of the myosin heads on the filament would not always interact with the actin filament. Thus, the myosin step size is considerably larger than the length of a power stroke expected from the physical size of a myosin head, 10-20 nm (Huxley, 1957, 1969).
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PMID:Movement of single myosin filaments and myosin step size on an actin filament suspended in solution by a laser trap. 801 9

The force developed by a muscle during steady shortening is due to cyclic interactions between the cross-bridges extending from the thick myosin filament to the thin actin filament. Each interaction consists of a power stroke of the myosin molecule that accounts for a limited amount of sliding between the two sets of filaments (about 12 nm according to quick release experiments), and is widely believed to be coupled to the hydrolysis of one ATP molecule. On the other hand both energetics studies in muscle and in vitro motility assays, indicating that shortening per ATP split is much larger than 12 nm, postulate that during shortening cross-bridges interact at a rate much faster than the ATP splitting rate. In the experiments reported here, made on intact fibres from frog skeletal muscle, the rate of regeneration of the power stroke was determined. Tension transients were elicited by imposing test step releases at different times (2-20 ms) after a conditioning release of about 5 nm. When the test step was imposed at 2 ms after the conditioning step, the tension attained at the end of the quick phase of recovery (T2, due to the force generating stroke of the attached cross-bridges) was depressed and the T2 curve (the plot of T2 tension versus size of the test step) intercepted the length axis to the right, with respect to the intercept of the control T2 curve, by an amount similar to the size of the conditioning step. By increasing the interval between conditioning and test step the T2 tension increased progressively and the T2 curve intercept approached the intercept of the control curve with a time constant of 6-7 ms. These results indicate that the force generating stroke elicited by a shortening step is followed by a relatively rapid process of detachment and reattachment by most of the cross-bridges, allowing for the generation of another power stroke. The rate of this process, 150/s, is one order of magnitude higher than that expected from the ATPase rate, suggesting that several actomyosin interactions occur in shortening muscle by the time one ATP is split. The results are stimulated with a mechanical kinetic model of contraction, in which, for a critical amount of shortening, cross-bridges can detach, rapidly reattach and generate force before the completion of the "normal" isometric cycle.
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PMID:Kinetics of regeneration of cross-bridge power stroke in shortening muscle. 810 79

The elementary events in energy transduction by the actomyosin motor, driven by ATP hydrolysis, were directly recorded from multiple and single molecules using a recently developed technique for nano-manipulation of single actin filaments by a microneedle. In order to avoid the effects of random orientation of myosin and association of myosin with an artificial substrate in the surface motility assay, we used single myosin-rod cofilaments with various ratios. Distinct actomyosin attachment, force generation (the power stroke) and detachment events were detected at a very low myosin: rod ratio. At high load, one power stroke generated 5-6 pN peak force and 2.3 pN force averaged over the cycle, which were compatible with those deduced from noise analysis of force fluctuations caused by multiple molecules. As the load was reduced, the length of the power stroke increased. At near zero load, the length of a power stroke was approximately 17 nm. The results suggested that an ATPase cycle produces one power stroke at high load and many ones at low load.
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PMID:Single-molecule analysis of the actomyosin motor using nano-manipulation. 813 79

Our previous titration and cross-linking experiments showed that myosin subfragment 1 (S1) can bind to one or two monomers in F-actin [Andreev, O. A., & Borejdo, J. (1991) Biochem. Biophys. Res. Commun. 177, 350-356; (1992a) J. Muscle Res. Cell Motil. 13, 523-533; (1992b) Biochem. Biophys. Res. Commun. 188, 94-101]. In the present work we used a sedimentation method to extend these studies to equilibrium binding and a stopped flow method to investigate its kinetics. Both equilibrium and kinetic data indicated the existence of two different rigor complexes. On the basis of these data we developed a model which suggested that binding of S1 to F-actin occurred in two steps: (i) initial rapid binding to one monomer of F-actin, A + M<==>A.M and (ii) a consequent slow binding to a neighboring monomer, A.M + A<==>A.M.A, where A stands for actin and M for myosin subfragment 1. The second reaction can proceed only if the neighboring actin site is unoccupied. The model fit the equilibrium and kinetic binding data with equilibrium constants K1 = 6 x 10(6) M-1 and K2 = 4 and kinetic constants k+1 = 10.5 x 10(6) M-1 s-1, k-1 = 1.75 s-1, k+2 = 0.8 s-1, and k-2 = 0.2 s-1, where the subscripts refer to the reactions i and ii. These results corroborate our hypothesis that myosin head can make two types of complexes with F-actin and support our speculation that during a power stroke in contracting muscle a myosin head may first bind to one and then to two actins.
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PMID:Two different rigor complexes of myosin subfragment 1 and actin. 821 82

The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analyze the effects of treatments known to increase the survival of the animal without a clear effect on its hypertensive state. Stroke-prone spontaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solution were untreated or treated with one of two diuretics, indapamide (3 mg/kg per day) or hydrochlorothiazide (20 mg/kg per day), from 6 to 13 weeks of age. Phenotype was characterized by the immunolabeling of arteries with antibodies raised against a cellular form (EIIIA) of fibronectin, alpha-smooth muscle actin, and nonmuscle myosin. We demonstrated that phenotypes of smooth muscle cells of the SHRSP differ from those found in Wistar-Kyoto rats. The difference in phenotype is specific for the vessel type: ie, an increased expression of nonmuscle myosin in the aorta and of both EIIIA fibronectin and nonmuscle myosin in the coronary arteries. The two diuretics (1) had no effect on blood pressure, (2) prevented or did not prevent the increase in medial thickness, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that in SHRSP the changes in the phenotype of smooth muscle cells and the thickness of arteries are unrelated events. We propose that the maintenance of the contractile phenotype of the arterial smooth muscle cells could be an essential parameter involved in the prevention of the deleterious consequences characteristic of a severe hypertensive state.
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PMID:Arterial smooth muscle cell phenotype in stroke-prone spontaneously hypertensive rats. 822 26

Changes of ischemic myocardium following coronary occlusion, including active and passive functions, and adaptive changes of non-ischemic surviving myocardium have been summarized under the term "left ventricular remodeling" post myocardial infarction. An increase in left ventricular volume may be a consequence, and associated with an adverse prognosis. Although left ventricular dilatation may increase stroke volume and, thus, be compensatory at first, in about one-fifth of patients it ultimately results in progressive dysfunction and heart failure. Major determinants of this process are time, infarct size, infarct location, global left ventricular function assessed 4 days after infarction by radionuclide ejection fraction and right heart catheter (stroke volume), and morphology of the infarct-associated coronary artery. The surviving myocardium hypertrophies and may also dilate structurally. Depression of left ventricular ejection fraction chronically after the infarct is due to deterioration of wall motion of chamber segments initially classified normal by radionuclide analysis. Biochemical changes may also occur, including reduction of phosphocreatine, prolongation of time to peak Cai2+, and changes in myosin isoforms. Systemic or local humoral factors may be involved in these changes, however, clear evidence is still lacking. Perfusion of surviving myocardium may be altered under various conditions due to morphologic and functional changes of coronary vasculature. Successful prevention of heart failure and death by angiotensin converting enzyme inhibitors in asymptomatic patients with left ventricular dysfunction post-myocardial infarction has supported the pathophysiologic concepts of remodeling.
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PMID:Ventricular remodeling after myocardial infarction. Experimental and clinical studies. 835 28


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