title: Eccentric contractions do not induce rhabdomyolysis in malignant hyperthermia susceptible mice.
abstract: Recent studies suggest a link between exercise-induced rhabdomyolysis and mutations of the ryanodine receptor (RYR1) associated with malignant hyperthermia (MH). We hypothesized that MH-susceptible mice (RYR1Y522S/wt) would exhibit greater anterior crural muscle [tibialis anterior (TA) and extensor digitorum longus (EDL) muscles] damage and strength deficits following the performance of a single or repeated bouts of eccentric contractions compared with wild-type (WT) mice. After a single injury bout, RYR1Y522S/wt mice produced more isometric torque than WT mice immediately and 3 and 7 days postinjury. Moreover, EDL muscle isometric specific force deficits were fully recovered for RYR1Y522S/wt but not WT mice 14 days postinjury. The percentage of fibers in TA muscle exhibiting signs of muscle damage 7 and 14 days postinjury were at least three times less in RYR1Y522S/wt than in WT mice. Uninjured and injured EDL muscle from RYR1Y522S/wt mice also displayed greater S-glutathionylation of RYR1 than that from WT mice. During the weekly injury bouts, torque production by RYR1Y522S/wt mice was fully recovered before the third and fourth injury bouts, whereas torque was still reduced for WT mice. Three days after multiple injury bouts, there were approximately 50% fewer fibers exhibiting signs of muscle damage in RYR1Y522S/wt than in WT TA muscle. These findings indicate that the RYR1Y522S/wt mutation protects skeletal muscle from exercise-induced muscle injury and do not support a direct association between MH susceptibility and contraction-induced rhabdomyolysis when core temperature is maintained at lower physiological temperatures during exercise.
authors.affiliation: Muscle Biology Laboratory, Department of Kinesiology and Health, Georgia State University, Atlanta, GA 30302-3975, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Corona
authors.forename: Clement
authors.initials: C
authors.lastname: Rouviere
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hamilton
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ingalls
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005978:Glutathione / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D008305:Malignant Hyperthermia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D010084:Oxidation-Reduction; D010641:Phenotype; D012206:Rhabdomyolysis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D019415:Torque
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D005978:Glutathione
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