@article{2d521da0eac711dc86ef000ea68e967b,
title = "Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?",
abstract = "Prolonged or unaccustomed exercise leads to muscle cell membrane damage, detectable as release of the intracellular enzyme lactic acid dehydrogenase (LDH). This is correlated to excitation-induced influx of Ca2+, but it cannot be excluded that mechanical stress contributes to the damage. We here explore this question using N-benzyl-p-toluene sulfonamide (BTS), which specifically blocks muscle contraction. 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 15-60 min or exposed to the Ca2+ ionophore A23187. Electrical stimulation increased 45Ca influx 3-5 fold. This was followed by a progressive release of LDH, which was correlated to the influx of Ca2+. BTS (50 microM) caused a 90\% inhibition of contractile force but had no effect on the excitation-induced 45Ca 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 Ca2+ 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 Ca2+ influx and energy status and not on mechanical stress.",
keywords = "Adenosine Triphosphate, Animals, Calcium, Cumulative Trauma Disorders, Electric Stimulation, Female, Isometric Contraction, Male, Muscle, Skeletal, Rats, Rats, Wistar, Stress, Mechanical",
author = "Anne Fredsted and Hanne Gissel and Klavs Madsen and Torben Clausen",
year = "2007",
month = jun,
day = "1",
doi = "10.1152/ajpregu.00415.2006",
language = "English",
volume = "292",
pages = "R2249--R2258",
journal = "American Journal of Physiology: Regulatory, Integrative and Comparative Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "6",
}