Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a highly variable clinical course and prognosis. We report on the cases of three siblings with SMA. The weakness Muscular observes at three siblings but more earlier and severe to the index case with a fast evolution towards respiratory distress syndrome resulting in its death at 5 years. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene were found in all three siblings. No child showed deletion of NAIP gene. Muscular weakness and respiratory distress severity however were different among the siblings. The index patient died at the age of 5 because of respiratory insufficiency. Several molecular mechanisms may be involved in such phenotypic variability. The PCR-RFLP method allows to confirm clinical diagnosis of SMA in children, while avoiding more invasive methods such as EMG and muscular biopsy. However, this diagnostic tool does not allow yet the distinction between different clinical forms of SMA. (C) 2008 Elsevier Masson SAS. All rights reserved.

The plasma membranes of chick or rat skeletal muscles, grown in cell culture, were made permeable with saponin in a solution lacking calcium. The cells were then supplied with a medium resembling the cytosol and the ATP-dependent Ca2+ sequestration was performed. Based on the low concentration of free Ca2+ in the medium (below 5 microM), the presence of mitochondrial inhibitors and the effect of drugs that interfere with sarcoplasmic reticulum (SR) function, we assume that the measured Ca2+ accumulation expresses SR function on the saponin-treated myotubes. The development of the SR in muscle cultures is augmented as myogenesis proceeds and depends on its occurrence. Whereas creatine kinase activity is elevated immediately following cell fusion, there is a delay of at least 1 day between myoblast fusion and the increase in Ca2+ accumulation in the SR. Thyroxine or triiodothyronine caused an inhibition of Ca2+ accumulation in rat or chick muscle cultures. This inhibition could explain some of the muscle abnormalities caused by excess of thyroid hormones. A comparison was made between a white-type (fast) and heterogeneous muscle, differentiated in cell culture. There was no significant difference in SR function, indicating the important role of innervation in specifying the properties of muscle fiber types.

Thyroid hormones (TH) have previously been shown to alter the force and velocity of cardiac muscle contractions. To investigate the mechanism responsible for these alterations, excess amounts of thyroxine (T4, 1μM) were applied on rat heart cells grown in cell culture. We found the following biochemical alterations: a) 40% decrease in the myoglobin content within 2 days; b) 25% increase in the rate of Ca-uptake into sacroplasmic reticulum (SR) in myocytes following chemical skinning; and c) a two-fold increase in Na−K-ATPase activity measured by86Rb-uptake. These changes support our hypothesis that TH induce the transition of slow-twitch (“red”) muscles towards the fast-twitch (“white”) muscle type. This may explain the changes in contractile activity known to occur under TH influence.

Regulation of the AChR level, assayed by 125I-alpha-bungarotoxin binding, was studied in chick skeletal muscles differentiated in cell culture. Variety of agents known to affect muscle contractions and calcium distribution were investigated. Synthesis of AChR is enhanced by treatment of myotubes with several drugs known to inhibit spontaneous activity, such as tetrodotoxin or D 600. In contrast, a reduction of AChR levels occurs due to prolonged treatment with caffeine or carbamylcholine. Sodium dantrolene which inhibits Ca2+ release from the sarcoplasmic reticulum, causes 90% elevation in the level of receptors when applied for 48 hr. Furthermore, in a combination of treatments with dantrolene and carbamylcholine, the effect of the last one is almost abolished. Similarly, in a combined treatment of D 600 together with caffeine, the last one is more dominant and reduces the level of the receptors, inspite of inactivity of the myotubes. These experiments support the idea that cytosolic Ca2+ acts as an information carrier to activate/inactivate the machinery of receptor synthesis. We conclude that muscle activity is not the main factor regulating AChR synthesis, but that intracellular Ca2+ released from the sarcoplasmic reticulum is a necessary mediator for the decline in AChR synthesis, whereas Ca2+ accumulation in SR exerts the opposite effect: enhancement of receptor synthesis.

Studies were made on the effect of thyroid hormones on the level of acetylcholine receptors (AChR) in cultured rat skeletal muscle. Treatment of differentiated myotubes in vitro with thyroxine (T4; 2 X 10(-7) mol/l) for 2-3 days caused a marked decrease in the amount of AChR (P less than 0.05) and an increase in activity of Na+-K+-ATPase (P less than 0.05). There was no significant effect of hormone treatment on other muscle proteins, such as creatine kinase and acetylcholinesterase. Measurements of the turnover rate of AChR in T4-treated myotubes showed only a very slight effect of T4 on the rate of AChR degradation. To study the mechanism by which the hormone exerts its effect, muscle cells were labelled with radioactive amino acid and the rate of its incorporation into AChR protein was measured. The AChR was then isolated using anti-AChR antibodies. The specific activity of labelled AChR was lower in hormone-treated cells. These experiments suggest that the decreased level of AChR in response to thyroid hormone treatment is due to a partial suppression of receptor synthesis.

FEBS LettersVolume 88, Issue 2 p. 327-331 Full-length articleFree Access The appearance of acetylcholine receptors triggered by fusion of myoblasts in vitro A. Shainberg, A. Shainberg Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this authorH. Brik, H. Brik Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this author A. Shainberg, A. Shainberg Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this authorH. Brik, H. Brik Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this author First published: April 15, 1978 https://doi.org/10.1016/0014-5793(78)80204-XCitations: 22AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 A. Shainberg, G. Yagil, D. Yaffe, Dev. Biol., 25, (1971), 1– 29. 2 T.G. Easton, E. Reich, J. Biol. Chem., 247, (1972), 6420– 6431. 3 B. Paterson, R.C. Strohman, Dev. Biol., 29, (1972), 113– 138. 4 H. Holtzer, J.M. Marshall, H. Finck, J. Cell. Biol., 3, (1957), 705– 723. 5 D. Fambrough, J.E. Rash, Dev. Biol., 26, (1971), 55– 68. 6 D.C. Turner, V. Maier, H.M. Eppenberger, Dev. Biol., 37, (1974), 63– 89. 7 D.C. Turner, R. Gmur, M. Siegrist, E. Burckhardt, H.M. Eppenberger, Dev. Biol., 48, (1976), 258– 283. 8 D.C. Turner, R. Gmur, H.G. Lebherz, M. Siegrist, T. Wallimann, H.M. Eppenberger, Dev. Biol., 48, (1976), 284– 307. 9 J.M. Keller, M. Nameroff, Differentiation, 2, (1974), 19– 23. 10 J.P. Merli, F. Gros, Exp. Cell. Res., 97, (1976), 406– 412. 11 P.S. Moss, R.C. Strohman, Dev. Biol., 48, (1976), 431– 437. 12 B.M. Vertal, D.A. Fischman, Dev. Biol., 48, (1976), 438– 446. 13 B. Paterson, J. Prives, J. Cell. Biol., 59, (1973), 241– 245. 14 P.N. Devreotes, D.M. Fambrough, J. Cell. Biol., 65, (1975), 335– 358. 15 A. Shainberg, G. Yagil, D. Yaffe, Exp. Cell. Res., 58, (1969), 163– 167. 16 A. Shainberg, S.A. Cohen, P.G. Nelson, Pflugers Arch. Eur. J. Physiol., 361, (1976), 255– 261. 17 G.L. Ellmann, K.D. Courtney, V. Andres, R.M. Featherstone, Biochem. Pharmacol., 1, (1961), 88– 95. 18 N.N.H. Teng, M.Y. Fiszman, J. Supramol. Struct., 4, (1976), 381– 387. 19 D. Yaffe, H. Dym, Cold Spring Harbor Symp. Quant. Biol., 37, (1972), 543– 547. Citing Literature Volume88, Issue2April 15, 1978Pages 327-331 ReferencesRelatedInformation