Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanical and biochemical descriptions of the muscle cross-bridge cycle have been correlated. Skinned muscle fibres of rabbit psoas muscle in rigor were incubated in solutions containing approximately equal to 30 microM-Ca2+ ions and P3-1-(2-nitro)phenylethyladenosine-5'-triphosphate, 'caged ATP', an inert photolabile precursor of ATP. ATP was liberated from caged ATP within the fibres by pulses of 347 nm radiation from a frequency-doubled ruby laser. The mechanical responses of muscle fibres to the rapid increase of ATP concentration were monitored. Tension dropped briefly and then rose above the rigor value to the level characteristic of a steady active contraction. Liberation of ATP decreased in-phase stiffness (measured at 500 Hz) from the rigor level to a maintained value intermediate between rigor and relaxed values. Out-of-phase stiffness increased to a maintained level indicating a phase lead of tension with respect to imposed length oscillations. Rigor tension was varied prior to photolysis by slight alterations of fibre length. Tension traces starting at different rigor tensions converged to a common tension level at the same rate, whether or not Ca2+ was included in the medium. These data suggest that the rate of cross-bridge detachment by ATP from the rigor state is not influenced by Ca2+. Analysis of the tension records, in terms of sequential detachment and reattachment reactions, provided a measure of cross-bridge reattachment rate and an alternate measure of the detachment rate. Detachment from the rigor state was approximately proportional to the ATP concentration, with a second-order rate constant of at least 5 X 10(5) M-1 S-1. Reattachment with force generation had no detectable dependence on the concentration of ATP liberated by photolysis. A simple kinetic model of the cross-bridge cycle in terms of chemically defined intermediates was compatible with most of the experimental data. The ATP dependence of cross-bridge detachment, the kinetics of maintained cross-bridge reattachment in the presence of Ca2+, and transient reattachment and final relaxation in the absence of Ca2+ were explained. In this model, reversibility of cross-bridge attachment and the steps leading to force production allow the relatively high observed detachment rate to be accommodated with other data relating to active contraction. These data include the steady ATPase rate of active muscle fibres and the fewer attached cross-bridges in active contractions compared to rigor.
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PMID:Initiation of active contraction by photogeneration of adenosine-5'-triphosphate in rabbit psoas muscle fibres. 648 46

Tension development, immediate stiffness and ATPase of chemically skinned myocardial strips were measured in solutions with varying concentrations of phosphate (Pi) or vanadate (predominantly H2VO4 at pH 7) ion. Vanadate and Pi decreased stiffness in proportion to tension. The results show that, like Pi, vanadate accelerates the turnover rate of cross-bridges, but is effective at about 1/500 the concentration required for the Pi effect. Both Pi and vanadate increased the energy cost of isometric tension maintenance (that is, the ratio of ATPase to tension) and increased the velocity of delayed tension development following quick stretch of the chemically skinned myocardial strips. The results also show that changes in the rate of rise of delayed tension during stretch activation probably reflect changes in the kinetics of the biochemical cycle of the cross-bridges.
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PMID:Vanadate and phosphate ions reduce tension and increase cross-bridge kinetics in chemically skinned heart muscle. 690 44

Soleus muscle atrophy was induced by hind-limb suspension of rats for 3 weeks with the intention of inducing a relative increase in the percentage of fast-twitch fibres and assessing modifications in muscle stiffness. A method of dual controlled releases was used to obtain tension/extension curves and force/velocity relationships characterizing the mechanical behaviour of the soleus. Fibre typing was achieved by myofibrillar adenosine 5'-triphosphatase staining. Results showed that hindlimb suspension decreased the percentage of slow-twitch fibres (-31%) to the profit of fast-twitch fibres (+370%) and intermediate fibres (+255%). This led to an increase in maximal shortening velocity. Tension/extension curves indicated a decrease in soleus stiffness after 3 weeks of unloading. Changes in elastic properties are interpreted in terms of modifications occurring in the active part and the passive part of the so-called series elastic component. These changes also suggest that the parameters derived from a twitch are inappropriate to account for modifications in speed-related properties of muscle.
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PMID:Changes in stiffness induced by hindlimb suspension in rat soleus muscle. 776 Dec 57

2,3-butanedione 2-monoxime (BDM) inhibits muscle contraction and actomyosin ATPase both in fibres and in solution. It is potentially useful as a tool for exploring weak interactions between actin and myosin. We have examined the effect of BDM on several key steps of the myosin subfragment-1 and actomyosin subfragment-1 ATPase in solution. These studies show that BDM shifts the equilibrium between two actomyosin states towards a more weakly bound form when the acto.myosin complex has ADP alone or ADP and phosphate bound. We also confirm the findings of Herrmann and colleagues (1993, Biochemistry, 31, 12227-32) that the main effect of BDM on the myosin subfragment-1 ATPase is to slow the release of phosphate following ATP hydrolysis. Skinned fibre studies show that the effects of BDM and phosphate on the steady isometric tension of the fibres are additive. This is consistent with the interpretation that BDM is reducing fibre tension either by increasing phosphate binding or by a direct effect on the crossbridge. Tension transients induced by rapid pressure release were examined in single muscle fibres; they showed that BDM reduces the rate of tension generation following pressure release. This result suggest that BDM directly affects the force generating event in the crossbridge.
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PMID:The influence of 2,3-butanedione 2-monoxime (BDM) on the interaction between actin and myosin in solution and in skinned muscle fibres. 792 96

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

Under normal conditions the cardiac output is designed to meet the metabolic needs of the organism. Thus, the demands imposed on the heart muscle can range from low values at rest to an order of magnitude greater values during exercise. The heart uses a number of strategies to meet the short- and long-term changes in demand. These strategies are of general biological interest and employ similar mechanisms to those responsible for the differences in muscle performance seen between muscle from various species and diverse muscle types within a given animal. This review deals with the heart's utilization of these strategies to meet a broad range of requirements. Tortoise (TM) and rat soleus (RS) muscles are slow, have high economy and develop low power. In contrast (FM) and rat extensor digitorum longus (REDL) are fast, have low economy and have a high power output. These differences are explainable in terms of the characteristics of the myosin head cross-bridge cycle (Cross-bridge tension-time integral: FM/FT = 0.024; REDL/RS = 0.16. Myosin ATPase activity: FM/TM = 15; RDEL/RS = 2.3) and excitation contraction coupling system (time to peak tension: FM/TM = 0.2; REDL/RS = 0.4). Heart muscle employs similar strategies (cross-bridge cycle; excitation contraction coupling) to meet short (catecholamine) and long (hypertrophy secondary to pressure overload or thyrotoxicosis) term changes in demand. In the presence of catecholamine power is increased while economy is decreased. This difference between control (C) and isoproterenol treated hearts (I) is explainable in terms of the contractile and excitation contraction coupling systems (Cross-bridge tension-time integral: I/C = 0.4. Tension independent heat: I/C = 2.0. Tension independent heat rate: I/C = 2.5). A persistent increase in the demand on the heart results in myocardial hypertrophy that is associated with intracellular reorganization. Hyperthyroidism (T) and pressure overload (PO) were used to produce myocardial hypertrophy. In T hearts the economy is decreased while the power is increased; in PO hearts oppositely directed changes occur. These alterations are attributable to changes in the performance of the contractile and excitation contraction coupling systems (Cross-bridge force-time integral: T/C/PO = 0.5/1.0/2.6. Tension independent heat: T/C/PO = 1.4/1.0/0.4. Tension independent heat rate: T/C/PO = 1.4/1.0/0.3). Thus it is clear that in meeting changes in demand, the heart uses strategies comparable to those seen between species and muscle types within a given muscle.
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PMID:Optimization of myocardial function. 814 34

To relate transients of force by single kinesin molecules with the elementary steps of the ATPase cycle, we measured the time to force generation by kinesin after photorelease of ATP from caged ATP. Kinesin-coated beads were trapped by an infrared laser and brought onto microtubules fixed to a coverslip. Tension was applied to a kinesin-microtubule rigor complex using the optical trap, and ATP was released by flash photolysis of caged ATP with a UV laser. Kinesin started to generate force and move stepwise with a step size of 8 nm at average times of 31, 45, and 79 ms after photorelease of 450, 90, and 18 microM ATP, respectively. The kinetics of force generation were consistent with a two-step reaction: ATP binding, with an apparent second-order rate constant of 0.7 microM-1.s-1, followed by force generation at 45 s-1 per kinesin molecule. The transient rate of force generation was close to the rate of the ATPase cycle in solution, suggesting that the rate-limiting step of ATPase cycle is involved with the force generation.
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PMID:Kinetics of force generation by single kinesin molecules activated by laser photolysis of caged ATP. 911

This study was undertaken to correlate some of the functional characteristics with the myofibrillar composition in myosin heavy chain isoforms on newborn and adult rat soleus muscles. The following postnatal ages were chosen in order to determine the role of innervation in the establishment of the mature muscle phenotype: before (postnatal day 6), when (postnatal day 12), and after (days 17 and 23) the monosynaptic innervation appeared. The steady state of definitive innervation was controlled on adult muscles (i.e. approximately 13 weeks). Muscle maturation was followed by ATPase staining and fibre diversity was observed at postnatal day 12. The functional properties of skinned bundles isolated from newborn rats were determined by Calcium/Strontium activation characteristics (Tension/pCa and pSr relationships). From postnatal days 6 to 17, the Soleus bundles exhibited Calcium/Strontium activation characteristics intermediate between slow and fast fibre populations previously described in muscles. At day 23, the Calcium/Strontium activation characteristics of the soleus were closer to those of a slow type. Moreover, we observed a decrease in Ca affinity concomitant with the installation of the monosynaptic innervation, and an increase of the slow type I during postnatal development. Finally, this work reported a greater correlation between the Calcium/Strontium activation parameters and the myosin heavy chain isoform composition at the postnatal days when the mature monosynaptic innervation pattern occurred.
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PMID:Contractile properties and myosin heavy chain composition of newborn rat soleus muscles at different stages of postnatal development. 914 95

1. The rate of appearance of inorganic phosphate (Pi) and hence the ATPase activity of rabbit psoas muscle in single permeabilized muscle fibres initially in rigor was measured following laser flash photolysis of the P3-1-(2-nitrophenyl)ethyl ester of ATP (NPE-caged ATP) in the presence and absence of Ca2+. Pi appearance was monitored from the fluorescence signal of a Pi-sensitive probe, MDCC-PBP, a coumarin-labelled A197C mutant of the phosphate-binding protein from Escherichia coli. Fibres were immersed in oil to optimize the fluorescence signal and to obviate diffusion problems. The ATPase activity was also measured under similar conditions from the rate of NADH disappearance using an NADH-linked coupled enzyme assay. 2. On photolysis of NPE-caged ATP in the presence of Ca2+ at 20 degrees C, the fluorescence increase of MDCC-PBP was non-linear with time. ATPase activity was 41 s-1 in the first turnover based on a myosin subfragment 1 concentration of 150 microM. This was calculated from a linear regression of the fluorescence signal reporting 20-150 microM of Pi release. Tension was at 67% of its isometric level by the time 150 microM Pi was released. ATPase activities were 36 and 31 s-1 for Pi released in the ranges of 150-300 microM and 300-450 microM, respectively. The ATPase activity had a Q10 value of 2.9 based on measurements at 5, 12 and 20 degrees C. 3. An NADH-linked assay showed the ATPase activity had a lower limit of 12.7 s-1 at 20 degrees C. The response to photolytic release of ADP showed that the rate of NADH disappearance was partially limited by the flux through the coupled reactions. Simulations indicated that the linked assay data were consistent with an initial ATPase activity of 40 s-1. 4. On photolysis of NPE-caged ATP in the absence of Ca2+ the ATPase activity was 0.11 s-1 at 20 degrees C with no discernible rapid transient phase of Pi release during the first turnover of the ATPase. 5. To avoid the rigor state, the ATPase rate in the presence of Ca2+ was also measured on activation from the relaxed state by photolytic release of Ca2+ from a caged Ca2+ compound, nitrophenyl-EGTA. At 5 degrees C the ATPase rate was 5.8 and 4.0 s-1 in the first and second turnovers, respectively. These rates are comparable to those when NPE-caged ATP was used. 6. The influence of ADP and Pi on the ATPase activities was measured using the MDCC-PBP and NADH-linked assays, respectively. ADP (0.5 mM) decreased the initial ATPase rate by 23%. Pi (10 mM) had no significant effect. Inhibition by ADP, formed during ATP hydrolysis, contributed to the decrease of ATPase activity with time. 7. The MDCC-PBP assay and NPE-caged ATP were used to measure the ATPase rate in single permeabilized muscle fibres of the semitendinosus muscle of the frog. At 5 degrees C in the presence of Ca2+ the ATPase activity was biphasic being 15.0 s-1 during the first turnover (based on 180 microM myosin subfragment 1). Tension was 74% of its isometric level by the time 180 microM Pi was released. During the third turnover the ATPase rate decreased to about 20% of that during the first turnover. 8. ATPase activity in isometric rabbit muscle fibres during the first few turnovers is about an order of magnitude greater than that when a steady state is reached. Possible reasons and the consequences for understanding the mechanism of muscular contraction are discussed.
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PMID:ATPase kinetics on activation of rabbit and frog permeabilized isometric muscle fibres: a real time phosphate assay. 917 99

Calponin is a thin filament-associated protein which has been implicated in the modulation of the contractile state of smooth muscle via its interaction with actin and inhibition of the actin-activated myosin Mg-ATPase. This inhibitory effect is alleviated by phosphorylation of calponin at Ser175 in vitro by protein kinase C. The issue of calponin phosphorylation in intact smooth muscle in response to agonists that activate protein kinase C is controversial. We have produced a monoclonal antibody that specifically recognizes calponin phosphorylated at Ser175 and used it to analyze calponin phosphorylation in porcine coronary arterial smooth muscle stimulated with prostaglandin F2alpha or phorbol 12,13-dibutylate (PDB). Calponin phosphorylation increased rapidly in response to prostaglandin F2alpha concomitant with the increase in tension. Calponin was then dephosphorylated while force was maintained. Tension development in response to PDB was significantly slower, but again calponin phosphorylation paralleled force development. In this case, calponin dephosphorylation was very slow, consistent with prolonged activation of protein kinase C. The protein kinase inhibitors, HA1077 (1-5-(isoquinoline sulfonyl)-homopiperazine HCl) and HA1100 (1-hydroxy HA1077; 1-(hydroxy-5-isoquinoline sulfonyl-homopiperazine), inhibited tension development and calponin phosphorylation in a concentration-dependent manner with similar ED50 values in response to prostaglandin F2alpha and PDB. These results support physiological roles for calponin in force development in smooth muscle in response to agonists which trigger protein kinase C activation and in the latch state, i.e., force maintenance at low energy cost. Furthermore, the vasodilator effect of HA1077 and HA1100 is more likely due to inhibition of protein kinase C than of myosin light chain kinase.
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PMID:HA1077, a protein kinase inhibitor, inhibits calponin phosphorylation on Ser175 in porcine coronary artery. 985 93


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