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Skeletal muscle function is dependent on its highly regular structure. In studies of dystrophic (dy/dy) mice, the proportion of malformed myofibers decreases after prolonged whole muscle stimulation, suggesting that the malformed myofibers are more prone to injury. The aim of this study was to assess morphology and to measure excitation-contraction (EC) coupling ([Ca.sup.2+] transients) and susceptibility to osmotic stress ([Ca.sup.2+] sparks) of enzymatically isolated muscle fibers of the extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles from young (2-3 mo) and old (8-9 mo) mdx and age-matched control mice (C57BL10). In young mdx EDL, 6% of the myofibers had visible malformations (i.e., interfiber splitting, branched ends, midfiber appendages). In contrast, 65% of myofibers in old mdx EDL contained visible malformations. In the mdx FDB, malformation occurred in only 5% of young myofibers and 11% of old myofibers. Age-matched control mice did not display the altered morphology of mdx muscles. The membrane-associated and cytoplasmic cytoskeletal structures appeared normal in the malformed mdx myofibers. In mdx FDBs with significantly branched ends, an assessment of global, electrically evoked [Ca.sup.2+] signals (indo-1PE-AM) revealed an EC coupling deficit in myofibers with significant branching. Interestingly, peak amplitude of electrically evoked [Ca.sup.2+] release in the branch of the bifurcated mdx myofiber was significantly decreased compared with the trunk of the same myofiber. No alteration in the basal myoplasmic [Ca.sup.2+] concentration (i.e., indo ratio) was seen in malformed vs. normal mdx myofibers. Finally, osmotic stress induced the occurrence of [Ca.sup.2+] sparks to a greater extent in the malformed portions of myofibers, which is consistent with deficits in EC coupling control. In summary, our data show that aging mdx myofibers develop morphological malformations. These malformations are not associated with gross disruptions in cytoskeletal or t-tubule structure; however, alterations in myofiber [Ca.sup.2+] signaling are evident. calcium; muscular dystrophy; skeletal muscle

Skeletal muscle function is dependent on its highly regular structure. In studies of dystrophic (dy/dy) mice, the proportion of malformed myofibers decreases after prolonged whole muscle stimulation, suggesting that the malformed myofibers are more prone to injury. The aim of this study was to assess morphology and to measure excitation-contraction (EC) coupling (Ca2+ transients) and susceptibility to osmotic stress (Ca2+ sparks) of enzymatically isolated muscle fibers of the extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles from young (2-3 mo) and old (8-9 mo) mdx and age-matched control mice (C57BLIO). In young mdx EDL, 6% of the myofibers had visible malformations (i.e., interfiber splitting, branched ends, midfiber appendages). In contrast, 65% of myofibers in old mdx EDL contained visible malformations. In the mdx FDB, malformation occurred in only 5% of young myofibers and 11% of old myofibers. Age-matched control mice did not display the altered morphology of mdx muscles. The membrane-associated and cytoplasmic cytoskeletal structures appeared normal in the malformed mdx myofibers. In mdx FDBs with significantly branched ends, an assessment of global, electrically evoked Ca2+ signals (indo-IPE-AM) revealed an EC coupling deficit in myofibers with significant branching. Interestingly, peak amplitude of electrically evoked Ca2+ release in the branch of the bifurcated mdx myofiber was significantly decreased compared with the trunk of the same myofiber. No alteration in the basal myoplasmic Ca2+ concentration (i.e., indo ratio) was seen in malformed vs. normal mdx myofibers. Finally, osmotic stress induced the occurrence of Ca2+ sparks to a greater extent in the malformed portions of myofibers, which is consistent with deficits in EC coupling control. In summary, our data show that aging mdx myofibers develop morphological malformations. These malformations are not associated with gross disruptions in cytoskeletal or t-tubule structure; however, alterations in myofiber Ca2+ signaling are evident. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia (MH) crises may induce morbidity or death in MH-susceptible (MHS) individuals. The only sensitive method of determining susceptibility is the caffeine-halothane contracture test, requiring muscle biopsy. Early research on MH demonstrated an abnormal response to catecholamines in MHS individuals. The purpose of this study was to determine whether MHS B lymphocytes would demonstrate an increased sensitivity to norepinephrine as indicated by an adrenergic augmentation of intracellular calcium ion (Ca 2+ ) accumulation, to possibly develop a less invasive laboratory assay for determining MH susceptibility. The fluorescent Ca 2+ indicator dye fura-2 acetoxymethyl was used to identify Ca 2+ flux within Epstein-Barr virus- immortalized MH-negative (MHN) and MHS B cells exposed to the RyR1 agonist 4-chloro-m-cresol (4-CmC) before and after administration of 1 μM of norepinephrine. In the presence of 4-CmC and norepinephrine, the area under the curve dose responses were significantly elevated in MHS B cells compared with MHN B cells (F[1,10] = 27.37; P < .01). Epstein-Barr virus-immortalized B cells from MHS humans displayed an increased sensitivity to norepinephrine compared with those from MHN individuals. These data suggest that an abnormal response to exogenous norepinephrine could potentially be used to develop a diagnostic laboratory assay to determine MH susceptibility., Competing Interests: The authors have declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)