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

The beneficial effect of low pH during cardiac ischemia on reperfusion injury has often been attributed to its energy-saving effect due to inhibition of contraction. The role of low pH on Ca2+ accumulation and muscle tension was assessed in energy-depleted tissue by changing the pH of the medium from 7.4 to 6.2 at onset of rigor development during metabolic inhibition (MI), i.e., in the energy-depleted phase. Cytosolic free Ca2+ ([Ca2+]i) and intracellular H+ (pHi) were measured in rat trabeculae at 20 degrees C with fura 2 and 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, respectively, and tension was recorded. The preparations were energy depleted by stimulation at 1 Hz in glucose-free Tyrode solution with 2 mM NaCN. Rigor developed within 20 min, indicating energy depletion. Resting [Ca2+]i was followed during 50 min (group I) or 100 min (group II) of rigor, and recovery was followed for 60 min in glucose-containing Tyrode solution at 0.2-Hz stimulation. Resting [Ca2+]i rose within 50 min (group I) but stabilized in the 50- to 100-min period (group II). All preparations from group I (n = 5) resumed contraction in the recovery period but in group II (n = 10) 70% failed to recover, and [Ca2+]i remained elevated compared with those that recovered. An extracellular pH of 6.2, resulting in similar pHi, from onset of rigor development (group III) led to only a modest rise in [Ca2+]i during the 100-min rigor period, and all preparations resumed contraction after approximately 3 min in normal medium. ATP was very low in all groups at the end of MI but was still significantly lower in group II than in groups I and III. A beneficial energy-sparing effect of low pH during the rigor phase can therefore not be excluded. We conclude that 1) the capacity of trabeculae to recover from MI depends on the time period and magnitude of the [Ca2+]i rise in the energy-depleted phase and 2) low pH in energy-depleted trabeculae protects against Ca overload, improving recovery after normalization of perfusion conditions.
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PMID:Exposure of energy-depleted rat trabeculae to low pH improves contractile recovery: role of calcium. 773 52

Previous studies in isolated limbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischaemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of 20 pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 h and served as controls; 14 others underwent 6 h of complete infrarenal occlusion. Thereafter, embolectomy was simulated in eight pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In six other pigs, the composition of the reperfusate and the conditions of reperfusion were controlled during the first 30 min, followed by normal blood reperfusion. Some 6 h of infrarenal aortic occlusion leads to a severe decrease in high-energy phosphates and muscle temperature, together with a slight increase in creatine kinase and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive oedema developed, the tissue showed a marked decrease in oxygen consumption, glucose consumption, tissue ATP, total adenine nucleotides, muscle pH and total calcium in the femoral vein. Furthermore, a massive increase was seen in plasma creatine kinase concentration and potassium, together with the development of muscle rigidity. In sharp contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion resulted in normal water content, oxygen consumption, glucose consumption, flow and muscle rigidity. Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content, less tissue acidosis, markedly reduced creatine kinase release, and potassium release as compared with that of normal blood reperfusion. This study shows that 6 h of acute infrarenal aortic occlusion will result in severe reperfusion injury (postischaemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.
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PMID:Reperfusion injury in skeletal muscle: controlled limb reperfusion reduces local and systemic complications after prolonged ischaemia. 785 92

1. Ventricular trabeculae from rat heart were chemically skinned with Triton X-100, which disrupts all cellular membranes including the sarcoplasmic reticulum. In the effective absence of Ca2+ (10(-9) M), trabeculae developed a maintained rigor contracture when ATP was withdrawn from the bathing solution. 2. The final level of tension obtained following withdrawal of ATP was dependent upon the pH of the bathing solution during development of rigor. Rigor tension at pH 5.5 was 10.1 +/- 0.9% (n = 8, mean +/- S.E.M.) of that at pH 7.0. Bathing the preparation in alkaline solution increased rigor force. At pH 8.0, rigor force increased to 218 +/- 6.7% (n = 4) of control responses developed at pH 7.0. The rate of development of rigor tension increased as the pH of the bathing solution was increased. Once established, rigor tension was unaffected by subsequent changes in pH. These effects of pH were fully reversible within the range 5.5-8.0. 3. The final level of rigor tension was slightly reduced when inorganic phosphate (P(i)) was included in the bathing solution prior to withdrawal of ATP. P(i) concentrations of 10, 20 and 30 mM reduced rigor tension to 87 +/- 2, 83 +/- 3 and 82 +/- 4% respectively. There was no significant effect of P(i) on the rate of development of rigor. The effect of P(i) at pH 6.0 was not significantly different from that observed at the control pH of 7.0. 4. These results suggest that the fall of intracellular pH and, to a lesser extent, the rise in [P(i)] that occurs during ischaemia will partially inhibit the development of a rigor contracture.
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PMID:Effects of pH and inorganic phosphate on rigor tension in chemically skinned rat ventricular trabeculae. 796 60

Experiments are presented that probe the mechanism of contraction in normal activated muscle fibers and in heated rigor fibers. In activated fibers we subdivide the partial recovery of isometric tension during the Huxley-Simmons phase 2 into temperature-independent and temperature-dependent steps termed, respectively, phase 2fast and phase 2slow. Evidence is presented to show that phase 2fast arises from the perturbation of a damped elastic element in the cross-bridge and that phase 2slow is the manifestation of an endothermic, order-disorder transition responsible for de novo tension generation. These responses are common to both frog and rabbit fibers. The only difference between animals is that the kinetics of phase 2slow appears to scale with the working temperature of the muscle and not absolute temperature. Rigor fibers heated above the working temperature of the muscle contract. Tension generation is, as with activated fibers, endothermic. Tension transients following a laser temperature-jump of activated and heated rigor fibers are virtually indistinguishable on the basis of either the form or magnitude of the response. In length-jump experiments, tension recovery by heated rigor fibers consists of three exponentials with a tension-dependent rate for the medium speed step. Preliminary data indicate that the rigor cross-bridge operates over a distance of between 13.5 and 18 nm. Collectively, these data imply that tension generation in muscle arises from accessible conformational states in the proteins of the cross-bridge alone. ATP hydrolysis in active fibers and the heating of rigor fibers simply serve to shift these intrinsic conformational equilibria towards tension generation.
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PMID:Kinetic and physical characterization of force generation in muscle: a laser temperature-jump and length-jump study on activated and contracting rigor fibers. 810 64

This paper presents a number of separate results concerning crossbridge attachment: [1] X-ray diffraction from live bumble bee flight muscle shows a set of layer lines distinct from that of relaxed Lethocerus, in which the apparent myosin helix is shorter than that of the actin. [2] Rigor crossbridges of Lethocerus are not rotatable by stretch. [3] Rabbit and Lethocerus fibres in rigor relaxed by ATP at -35 degrees C show evidence of non-rigor crossbridge attachment.
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PMID:Inferences concerning crossbridges from work on insect muscle. 810 67

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.
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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.
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PMID:Flash and smash: rapid freezing of muscle fibers activated by photolysis of caged ATP. 836 45

Our previous studies in isolated rat hindlimbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in-vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 hours and served as controls. Fourteen other pigs underwent 6 hours of complete infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In 6 other pigs, control of the composition of the reperfusate and control of the conditions of reperfusion was done during the first 30 min, followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion lead to a severe decrease in high energy phosphates and muscle temperature and a slight increase in creating kinase (CK) and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p < 0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p < 0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001), total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p < 0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore, a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80 U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001) and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%), oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs. 4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1 degree). Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6 +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702 vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/- 0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion this study shows that 6 hours of acute infrarenal aortic occlusion will result in a severe reperfusion injury (postischemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.
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PMID:[Controlled reperfusion of the extremities for preventing local and systemic damage after prolonged ischemia. An experimental study with the swine model]. 901 38

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.
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PMID:Tomographic three-dimensional reconstruction of insect flight muscle partially relaxed by AMPPNP and ethylene glycol. 934 86

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.
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PMID:Modulation of rigor and myosin ATPase activity in rat cardiomyocytes. 971 Aug 3


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