Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)-ATP50 to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P < .001) and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg(2+)-ADP (250 mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P < .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to < 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal rigor tension developed to 143% of the control value; P(i) had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg(2+)-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.
 ...
PMID:Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness. 815 39

A new approach was used to study transient structural states of cross-bridges during activation of muscle fibers. Rabbit skinned muscle fibers were rapidly and synchronously activated from the rigor state by photolysis of caged ATP in the presence of Ca2+. At several different times during the switch from rigor to fully active tension development, the fibers were rapidly frozen on a liquid helium-cooled metal block, freeze-substituted, and examined in an electron microscope. The limits of structural preservation and resolution with this technique were analyzed. We demonstrate that the resolution of our images is sufficient to draw the following conclusions about cross-bridge structure. Rigor cross-bridges point away from the Z-line and most of them are wider near the thin filaments than near the backbone of the thick filaments. In contrast, cross-bridges in actively contracting fibers stretch between the thick and thin filaments at a variable angle, and are uniformly thin. Diffraction patterns computed from contracting muscle show layer lines both at 38 and 43 nm indicating that active cross-bridges contribute mass to both the actin- and myosin-based helical periodicities. The images obtained from fibers frozen 20 ms after release of ATP show a mixture of rigor and active type cross-bridge configurations. There is little evidence of cross-bridges with the rigor shape by 50 ms, and the difference in configurations between 50 and 300 ms after photolysis is surprisingly subtle.
 ...
PMID:Flash and smash: rapid freezing of muscle fibers activated by photolysis of caged ATP. 836 45

We examined the changes in adenosine triphosphate (ATP), lactic acid, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in five different rat muscles after death. Rigor mortis has been thought to occur simultaneously in dead muscles and hence to start in small muscles sooner than in large muscles. In this study we found that the rate of decrease in ATP was significantly different in each muscle. The greatest drop in ATP was observed in the masseter muscle. These findings contradict the conventional theory of rigor mortis. Similarly, the rates of change in ADP and lactic acid, which are thought to be related to the consumption or production of ATP, were different in each muscle. However, the rate of change of AMP was the same in each muscle.
 ...
PMID:Reconsideration of the sequence of rigor mortis through postmortem changes in adenosine nucleotides and lactic acid in different rat muscles. 894 33

Muscle fibres in the rigor state and free of nucleotide contract if heated above their physiological working temperature. Kinetic studies on the mechanism of this process, termed rigor contraction, indicate that it has a number of features in common with the contraction of maximally Ca2+ activated fibres. De novo tension generation appears to be associated with a single, tension sensitive, endothermic step in both systems. Rigor contraction differs in that steps associated with crossbridge attachment and detachment are absent. We investigated structural changes associated with rigor contraction using X-ray diffraction. Overall changes in the low angle X-ray diffraction pattern were surveyed using a two-dimensional image plate. Reversible changes in the diffraction pattern included a 28% decrease in intensity of the 14.5 nm meridional reflection, a 12% increase in intensity of 5.9 nm actin layer-line and a somewhat variable 34% increase in intensity of 5.1 nm actin layer-line in laser temperature-jump experiments. When fibres were heated with a temperature ramp, we found that a 70% decrease in intensity of the myosin-related meridional reflection at (14.5 nm)-1 correlated with tension generation. A similar decrease in intensity of the 14.5 nm reflection is seen during tension recovery following a step change in the length of maximally Ca2+ activated fibres. Signals both from actin and actin-bound myosin heads contribute to the 5.1 and 5.9 nm actin layer-lines. Our observed changes in intensity are interpreted as contraction-associated changes in crossbridge shape and/or position on actin.
 ...
PMID:X-ray diffraction studies on thermally induced tension generation in rigor muscle. 899 81

Electrical and optical changes were measured in bovine sternomandibularis and porcine sternocephalicus strips tested sinusoidally in a rigorometer up to 3 h postmortem. Rigor development was detected by decreased muscle elongation, decreased stress-strain hysteresis area, and increased elastic modulus. Elastic modulus was affected by loading rate (r = .98, P < .005) from loading rates of 3.6 to 13.3 kPa/s. Capacitance decreased and resistance increased at 120 Hz, 1 kHz, and 10 kHz as rigor developed. Sometimes changes were irregular at one frequency but steady at another. The most consistent electrical predictors of rigor development were capacitance at 120 Hz and resistance at 10 kHz. Electrical impedance changed as muscle strips were stretched in the rigorometer, so that dimensional effects could be a source of error if testing causes muscle contraction. The dominant fiber-optic reflectance changes during rigor development were increases toward 400 nm and decreases toward 700 nm, although transient increases were sometimes detected toward 700 nm. Optical changes generally were later than electrical changes. All these complex changes are an obstacle to the early prediction of pH-dependent aspects of meat quality from electrical and optical measurements.
 ...
PMID:Observations on rheological, electrical, and optical changes during rigor development in pork and beef. 911 Feb 10

Rigor insect flight muscle (IFM) can be relaxed without ATP by increasing ethylene glycol concentration in the presence of adenosine 5'-[beta'gamma- imido]triphosphate (AMPPNP). Fibers poised at a critical glycol concentration retain rigor stiffness but support no sustained tension ("glycol-stiff state"). This suggests that many crossbridges are weakly attached to actin, possibly at the beginning of the power stroke. Unaveraged three-dimensional tomograms of "glycol-stiff" sarcomeres show crossbridges large enough to contain only a single myosin head, originating from dense collars every 14.5 nm. Crossbridges with an average 90 degrees axial angle contact actin midway between troponin subunits, which identifies the actin azimuth in each 38.7-nm period, in the same region as the actin target zone of the 45 degrees angled rigor lead bridges. These 90 degrees "target zone" bridges originate from the thick filament and approach actin at azimuthal angles similar to rigor lead bridges. Another class of glycol-PNP crossbridge binds outside the rigor actin target zone. These "nontarget zone" bridges display irregular forms and vary widely in axial and azimuthal attachment angles. Fitting the acto-myosin subfragment 1 atomic structure into the tomogram reveals that 90 degrees target zone bridges share with rigor a similar contact interface with actin, while nontarget crossbridges have variable contact interfaces. This suggests that target zone bridges interact specifically with actin, while nontarget zone bridges may not. Target zone bridges constitute only approximately 25% of the myosin heads, implying that both specific and nonspecific attachments contribute to the high stiffness. The 90 degrees target zone bridges may represent a preforce attachment that produces force by rotation of the motor domain over actin, possibly independent of the regulatory domain movements.
 ...
PMID:Tomographic three-dimensional reconstruction of insect flight muscle partially relaxed by AMPPNP and ethylene glycol. 934 86

The interaction between actin and myosin can be studied in the in vitro motility assay, where fluorescently labelled actin filaments are observed to move over a lawn of myosin heads. To examine details of this movement, we measured systematically the velocities of the front end, rear end, and centroid of the actin filament as the filament translated over the assay surface. We found that these velocities exhibited an unexpectedly periodic component, alternating regularly between high and low values, superimposed on the steady velocity component. The period of the oscillatory component was approximately 380 ms. When translation was stopped by an increase in osmolarity, the filaments wiggled with a periodicity similar to the translating filament, implying that wiggling and translation may be related. Rigor filaments showed no periodicity. From the frequency content of the auto- and cross-correlation functions derived from the velocities of the front end, rear end, and centroid of the actin filament, we infer a deterministic, possibly wave-like process travelling along the actin filament. Potential molecular mechanisms underlying this phenomenon are considered.
 ...
PMID:Actin-filament motion in the in vitro motility assay has a periodic component. 941 76

Ischaemic myocardium undergoes calcium-independent contracture at millimolar tissue ATP, though in actomyosin solutions ATP must be reduced to micromolar before rigor complexes form. This contracture is associated with myosin ATPase activity that may contribute to tissue de-energization. Here we used isolated rat cardiomyocytes permeabilized with digitonin to analyse in parallel how rigor and myosin ATPase activity are modulated by metabolic conditions that develop during ischaemia. At pH 7.1 and 37 degrees C rigor and myosin ATPase showed co-ordinated bell-shaped dependence on ATP concentration over 3-1000 microM. Rigor, but not myosin ATPase, was inhibited by acidosis (pH 6.2), indicating reduced efficiency of cross-bridge cycling, while both parameters were stimulated by ADP (< or = 1 mM) and unaffected by inorganic phosphate (Pi, 30 mM), AMP, Mg2+, lactate or inhibition of adenylate kinase with diadenosine pentaphosphate. Combined acidosis and high ADP inhibited rigor, while Pi attenuated the enhancement of rigor by ADP. Thus, rigor complex formation activates myosin ATPase in the intact myofilament array, modulated by ADP, Pi and acidosis in the ranges that occur in ischaemia. There was no evidence that adenylate kinase might attenuate falling ATP/ADP ratio at the myofilaments. In combination these effects are sufficient to resolve the apparent discrepancy between ATP concentrations triggering rigor in actomyosin and onset of contracture in ischaemic myocardium. Since rigor contracture activates myosin ATPase it is likely to exacerbate ATP depletion and thereby limit vital cell functions. This positive feedback is consistent with the abrupt depletion of ATP observed in individual cardiomyocytes undergoing deenergization contracture.
 ...
PMID:Modulation of rigor and myosin ATPase activity in rat cardiomyocytes. 971 Aug 3

1. The effect of thiophosphorylation of the regulatory myosin light chain (MLC20) on rigor stiffness was determined in permeabilized rabbit bladder smooth muscle. 2. Rigor stiffness of alpha-toxin-permeabilized smooth muscle was significantly increased by thiophosphorylation of MLC20. This increase may have been due to partial shortening (melting) in the proximal rod region and/or stiffening of the regulatory domain of the myosin head. 3. We suggest that phosphorylation of MLC20, by increasing the stiffness of the S1 lever arm and/or S2 hinge regions of the myosin molecule, favours separation of the two phosphorylated heads and consequent deinhibition of motor domain activity.
 ...
PMID:Thiophosphorylation of myosin light chain increases rigor stiffness of rabbit smooth muscle. 976 25

Structural and functional properties of intrastrand, ANP (N-(4-azido-2-nitrophenyl)-putrescine) cross-linked actin filaments, between Gln-41 and Cys-374 on adjacent monomers, were examined for several preparations of such actin. Extensively cross-linked F-actin (with 12% un-cross-linked monomers) lost at 60 degrees C the ability to activate myosin ATPase at a 100-fold slower rate and unfolded in CD melting experiments at a temperature higher by 11 degrees C than the un-cross-linked actin. Electron microscopy and image reconstruction of these filaments did not reveal any gross changes in F-actin structure but showed a change in the orientation of subdomain 2 and a decrease in interstrand connectivity. Rigor and weak (in the presence of ATP) myosin subfragment (S1) binding and acto-S1 ATPase did not show major changes upon 50% and 90% ANP cross-linking of F-actin; the Kd and Km values were little affected by the cross-linking, and the Vmax decreased by 50% for the extensively cross-linked actin. The cross-linking of actin (50%) decreased the mean speed and the number of sliding filaments in the in vitro motility assays by approximately 35% while the relative force, as measured by using external load in these assays, was inhibited by approximately 25%. The mean speed of actin filaments decreased with the increase in their cross-linking and approached 0 for the 90% cross-linked actin. Also examined were actin filaments reassembled from cross-linked and purified ANP cross-linked dimers, trimers, and oligomers. All of these filaments had the same acto-S1 ATPase and rigor S1 binding properties but different behavior in the in vitro motility assays. Filaments made of cross-linked dimers moved at approximately 50% of the speed of the un-cross-linked actin. The movement of filaments made of cross-linked trimers was inhibited more severely, and the oligomer-made filaments did not move at all. These results show the uncoupling between force generation and other events in actomyosin interactions and emphasize the role of actin filament structure and dynamics in the contractile process.
 ...
PMID:Intrastrand cross-linked actin between Gln-41 and Cys-374. III. Inhibition of motion and force generation with myosin. 992 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>