High cholesterol level and statin treatment affect the calcium homestasis of rat skeletal muscle cells

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD268

Poster Communications: High cholesterol level and statin treatment affect the calcium homestasis of rat skeletal muscle cells

J. Vincze1, M. Fuzi1, A. Jenes1, B. Dienes1, P. Szentesi1, P. Kertai2, G. Paragh3, L. Csernoch1

1. Department of Physiology, University of Debrecen, Debrecen, Hungary. 2. Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary. 3. Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.

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Statins are the most widely used drugs in the treatment of hyperlipidaemia. Their side-effects on skeletal muscle, however, have been reported with increasing frequency. Although the pathomechanism of the statin associated myopathy has been studied in detail and several theories do exist, there is still no final consensus. To study of the effects of statin on skeletal muscle rats were fed with a special diet to achieve high blood cholesterol levels and fluvastatin was administered to them orally. Single skeletal muscle fibers were isolated enzymatically from the extensor digitorum communis muscles of rats. The surface membrane was permeabilized using a relaxing solution containing saponin. Cells were then loaded with Fluo-4 and imaged using a Zeiss LSM 510 META laser scanning confocal microscope to study localized calcium release events. Images were automatically analysed using the method published by Szabó LZ et al. (2010). All data are presented as mean±S.E.M. Blood cholesterol levels of rats kept on a cholesterol-rich diet rose more than seven fold (from 1.5±0.1 to 10.7±2.0 mmol/L; n=15 and 16) with a dramatic increase in LDL/HDL ratio (from 0.29±0.02 to 1.56±0.17), proving that our model is usable for the study of hypercholesterolaemia. Previously published (Füzi et al. (2012)) elevation of the resting calcium level of adult skeletal muscle cells in both hypercholesterolemic and statin-treated rats was also accompanied by changes in the frequency of localized calcium release events (sparks). Muscle cells from statin-treated animals kept on normal cholesterol diet had higher spark frequency than cells from control animals (1.59 vs 0.88 s-1sarc-1) and cells from statin-treated animals kept on a high cholesterol diet had higher spark frequency than those from untreated hypercholesterolemic animals (1.48 vs 0.94 s-1sarc-1). Full width of half maximum values of sparks were slightly elevated and amplitude values were slightly decreased in all groups compared to the control. Fluvastatin and rosuvastatin were also applied on rat primary cell cultures to assess their effects on in vitro proliferation an differentiation. Effects on the cytoskeletal structure of muscle cells were visualized using immunofluorescence. Skeletal muscle cell proliferation and differentiation were impaired and a decrese in the level of fibrillar actin was seen in statin-treated cultures. The effects of statins on the calcium homeostasis, proliferation, differentiation and structure of adult and developing muscle cells may contribute to the explanation of certain adverse effects seen in clinical use.



Where applicable, experiments conform with Society ethical requirements.

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