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Extensor digitorum longus muscles were prepared from 4-wk-old rats and mounted on holders for isometric contractions. Muscles were stimulated intermittently at 40 Hz for 15\u201360 min or exposed to the Ca<jats:sup>2+<\/jats:sup>ionophore A23187. Electrical stimulation increased<jats:sup>45<\/jats:sup>Ca influx 3\u20135 fold. This was followed by a progressive release of LDH, which was correlated to the influx of Ca<jats:sup>2+<\/jats:sup>. BTS (50 \u03bcM) caused a 90% inhibition of contractile force but had no effect on the excitation-induced<jats:sup>45<\/jats:sup>Ca influx. After stimulation, ATP and creatine phosphate levels were higher in BTS-treated muscles, most likely due to the cessation of ATP-utilization for cross-bridge cycling, indicating a better energy status of these muscles. No release of LDH was observed in BTS-treated muscles. However, when exposed to anoxia, electrical stimulation caused a marked increase in LDH release that was not suppressed by BTS but associated with a decrease in the content of ATP. Dynamic passive stretching caused no increase in muscle Ca<jats:sup>2+<\/jats:sup>content and only a minor release of LDH, whereas treatment with A23187 markedly increased LDH release both in control and BTS-treated muscles. In conclusion, after isometric contractions, muscle cell membrane damage depends on Ca<jats:sup>2+<\/jats:sup>influx and energy status and not on mechanical stress.<\/jats:p>","DOI":"10.1152\/ajpregu.00415.2006","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T04:13:51Z","timestamp":1172808831000},"page":"R2249-R2258","source":"Crossref","is-referenced-by-count":22,"title":["Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?"],"prefix":"10.1152","volume":"292","author":[{"given":"Anne","family":"Fredsted","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne","family":"Gissel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klavs","family":"Madsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben","family":"Clausen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-199112030-00004"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.3.C825"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020943"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1993.74.3.1381"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006816123601"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.42.4.803"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03184"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020980"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/ncb734"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1977.sp011704"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1977.sp011958"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1991.71.3.733"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.50.2.255"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00500.2004"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Duncan CJ, Jackson MJ.Different mechanisms mediate structural changes and intracellular enzyme efflux following damage to skeletal muscle.J Cell Sci87: 183\u2013188, 1987.","DOI":"10.1242\/jcs.87.1.183"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1993.tb09512.x"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1992.262.5.E637"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1989.sp003318"},{"key":"R19","unstructured":"Fredsted A, Gissel H, Clausen T.Causes of stimulation-induced muscle cell damage: Mechanical strain or calcium overload? 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