Akio Takagi

Muscle glycogen metabolism in steroid-induced myopathy of rabbits.

Abstract Experimental myopathy was induced in rabbits by daily injections of triamcinolone. Glycogen concentration of lateral vastus increased from 5.3 to 12.5 mg/g in 7 days. Anerobic glycolysis in vitro was not significantly changed by steroid treatment. Total glycogen synthetase activity was increased 2.60 times and I form activity 1.74 times in 7 days. These results suggest that the increase in glycogen synthesis is a possible cause of accumulated glycogen in the affected muscle. The mechanism of the increased level of glycogen synthetase activity was also discussed.

Guinea pig soleus and extensor digitorum longus: A study on single-skinned fibers

Abstract Single-skinned fibers were prepared from soleus and extensor digitorum longus muscles of guinea pigs. Using the preparations, the regulation of contraction by calcium or strontium ion was compared. All fibers from soleus contracted at 10−6 m free Ca, whereas many extensor digitorum longus fibers did not at this concentration of free Ca. The difference in sensitivity to Ca ion, however, was slight. When Sr was the activating ion, the soleus developed tension at much lower concentrations than the extensor digitorum longus. The difference in sensitivity to Sr ion could be a criterion for fiber typing.

Increased leakage of calcium ion from the sarcoplasmic reticulum of the mdx mouse

Using a single skinned muscle fiber, the function of the contractile system and the sarcoplasmic reticulum (SR) were analyzed in the skeletal muscle of the mdx mouse. Activation of the contractile system by calcium ion and the maximum force generation was normal. Ca2+ uptake of the SR was normal as well as regulation of the Ca-induced Ca release (CICR) by Ca2+. However, contracture by caffeine was more prominent in mdx than in control mice. Ca2+ leaked more from the SR of mdx in the presence of EGTA and ATP or its analogue. These abnormalities are probably interrelated; increased leakage of Ca2+ might cause the enhanced response to caffeine, since Ca2+ itself facilitates Ca release by caffeine. The abnormal leakage of Ca2+ might also activate the Ca pump of SR in the resting state, which consume extra ATP and disturb energy metabolism.

Neuroleptic malignant syndrome Caffeine contracture of single muscle fibers and muscle pathology

The neuroleptic malignant syndrome (NMS) is similar to anesthesia-induced malignant hyperthermia (MH) in three major clinical features: hyperthermia, muscular rigidity, and myoglobinuria. In eight cases of NMS, we studied caffeine contracture of single skinned muscle fibers. Sensitivity of the sarcoplasmic reticulum to caffeine was abnormally increased in six of the eight cases. Morphologic studies showed type 2B fiber atrophy in all six cases examined, and there were necrotic fibers in two cases. Since skeletal muscle is affected in NMS, these patients may be susceptible to MH.

Dysfunction of sarcoplasmic reticulum in rabbit and human steroid myopathy.

Abstract Experimental steroid myopathy was induced in rabbits by injections of triamcinolone acetonide. Sarcoplasmic reticulum was prepared from quadriceps muscle. Calcium-dependent ATPase activity decreased in the steroid-treated group. Calcium uptake and binding of sarcoplasmic reticulum were also reduced in the steroid-treated group. By the same methods, sarcoplasmic reticulum in human steroid myopathy was analysed. Again, decreased calcium-dependent ATPase activity, calcium uptake, and binding were revealed in steroid myopathy. These results are consistent with the view that the effects of glucocorticoid on skeletal muscle are mediated, in part, through its action on the calcium transport system.

Single‐skinned human muscle fibers: Activation by calcium and strontium

Single-skinned fibers were prepared from human skeletal muscle. Tension generation was measured in solutions containing different amounts of free calcium or strontium ion. Fibers were classified into two types, on the basis of distinct differences in their regulation by strontium. One group developed maximal tension in 3 × 10−5 M free strontium, whereas the other developed minimal or no tension in the same concentration of strontium. It seemed most probable that the former represented type 1 (slow twitch) fiber and the latter type 2 (fast twitch) fiber because of similar patterns observed in guinea pig soleus and extensor digitorum longus muscle fibers.

Mounding phenomenon An experimental study in vitro

“Mounding” is a local contracture of skeletal muscle that is induced by tapping the muscle directly. We studied the mounding phenomenon in vitro on rat muscles that were percussed by a rotating hammer. In the bulged portion of muscle, there were scattered areas where the sarcomere length was shortened. After muscle was depolarized by the application of KC1-Ringer solution or relaxing solution, the mounding phenomenon was preserved. Agents that abolish the function of T-tubule or T-SR junction did not alter the phenomenon, either. However, after the function of intracellular membrane system such as the sarcoplasmic reticulum (SR) was destroyed by Brij 58, the mounding disappeared. Thus, the mounding is a local contracture that is probably induced by calcium ion liberated from the SR by percussion.

Chlorpromazine and skeletal muscle: a study of skinned single fibers of the guinea pig.

Abstract The effect of chlorpromazine (CPZ) on fast twitch muscle of the guinea pig was examined by using the skinned single-fiber preparation. The drug influenced the function of both the contractile system and the sarcoplasmic reticulum (SR). CPZ made the contractile system more sensitive to calcium ion, shifting the tension-pCa curve to the left, but it did not alter the maximal tension developed at a saturating concentration of Ca. CPZ elicited contracture of the fiber by releasing Ca ion from the SR. Calcium release by CPZ was inhibited either by procaine or magnesium ion and was facilitated when the medium contained more free Ca ion. These observations suggested that Ca release by CPZ was due to the activation of a Ca-induced Ca release mechanism. The effect of CPZ on Ca transport of the SR and its modification by Mg ion was quite equal in the absence of adenosine triphosphate as well as its presence. This indicates that the main site of action of CPZ is in the Ca release mechanism. A CPZ concentration greater than 0.3 m m damaged the function of the SR irreversibly.

Hereditary muscular atrophy with ataxia, retinitis pigmentosa, and diabetes mellitus: A clinical report of a family

A HEREDITARY DISORDER affecting 10 members of 4 generations of a kinship to be described here is characterized by neurogenic muscular atrophy associated with signs of cerebellar ataxia, degeneration of the retina, and diabetes mellitus (Fig. 1). This disease is similar to heredopathia atactica polyneuritiformis ( Refsum’s syndrome) ; however, there are some differences between them. Since this is considered to be a new clinical syndrome not hitherto described, it is the purpose of this report to present the clinical study of this disorder.

Muscular abnormalities in experimental hypothyroidism of rats with special reference to the mounding phenomenon

The mounding phenomenon was examined in vitro on the excised extensor digitorum longus or soleus muscle of hypothyroid rats. The mounding phenomenon was more prominent and lasted longer in hypothyroid muscles than in controls. In single skinned muscle fibers of both type 1 and type 2 from hypothyroid animals, the maximum tension produced by Ca ion was reduced and activity of Ca uptake by the sarcoplasmic reticulum was also decreased, judging from the response to caffeine. Decreased Ca uptake might retard the relaxation of contracture, thereby rendering the mounding more prominent. Morphological studies of both extensor digitorum longus and soleus muscles showed an increase of type 1 muscle fiber population as well as mild changes in arrangement of the internal membrane system. However, there was no muscle necrosis or other derangements. These results supported the idea that functional abnormality of the sarcoplasmic reticulum could be the basis of the exaggeration of the mounding phenomenon in hypothyroidism.