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 regulation of contractile activity in mice bearing a null mutation of the M-isoform of creatine kinase gene, has been investigated in tissue extracts and Triton X-100-treated preparations of ventricular, soleus, and gastrocnemius muscles of control and transgenic mice. Skinned fiber experiments did not evidence any statistical difference in the maximal force or the calcium sensitivity of either muscle type. Rigor tension development at a low MgATP concentration was greatly influenced by phosphocreatine in control but not in transgenic mice as should be expected. In calcium-activated ventricular preparations, although the force developed by each cross-bridge was the same in control and transgenic animals, the rate constant of tension changes appeared to be markedly slowed in transgenic animals. As the ventricular isomyosin pattern was not altered, we suggested that, in transgenic animals, cross-bridge cycling was hindered by a local decrease in the MgATP to MgADP ratio, due to lack of a local MgATP regenerating system. Myokinase activity was not significantly changed while activities of pyruvate kinase or glyceraldehyde-3-phosphate dehydrogenase were found to be increased in transgenic animals. These results show that no fundamental remodelling occurs in myofibrils of transgenic animals but that important adaptations modify the bioenergetic pathways including glycolytic metabolism.
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PMID:Muscle creatine kinase-deficient mice. I. Alterations in myofibrillar function. 765 6

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 In the effective absence of Ca2+ (10(-9) M), trabeculae developed a maintained rigor contracture when ATP was withdrawn from the bathing solution. 2.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

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