Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis.
Abstract: To determine whether abnormal regulation of muscle contraction similar to that associated with malignant hyperthermia (MH) was evident in intact external intercostal muscle cells from Thoroughbreds with recurrent exertional rhabdomyolysis (RER). Methods: 5 adult Thoroughbred horses with RER and 7 clinically normal adult Thoroughbred or mixed-breed horses. Methods: Twitch time course variables and contracture responses to various concentrations of potassium, caffeine, and halothane were measured in small bundles of intact external intercostal muscle cells from clinically normal horses and horses with RER. Results: Threshold for significant contracture induced by potassium depolarization was lower for RER-affected muscles, compared with normal muscles, although the relationship between potassium concentration and membrane potential were not different. Thresholds for contracture induced by caffeine and halothane were also lower for RER-affected muscles, compared with normal muscles. Lower thresholds for caffeine- and halothane-induced contractures, as well as depolarization-elicited contractures, in RER-affected muscles suggest a defect in myoplasmic calcium regulation. Conclusions: Regulation of muscle contraction is abnormal in Thoroughbreds with RER. The specific defect may be attributable to abnormal intracellular calcium regulation. Knowledge of the specific defect involved in RER may lead to improved prevention and treatment of RER-affected horses.
Publication Date: 1999-08-18 PubMed ID: 10451211
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study investigates if Thoroughbred horses with recurrent exertional rhabdomyolysis (RER) have abnormal muscle regulation similar to malignant hyperthermia (MH). Their research suggests that Thoroughbreds with RER have an abnormality in the regulation of muscle contraction, which may be related to defective intracellular calcium regulation.
Methods and subjects of the study
- The researchers conducted this study on 5 adult Thoroughbred horses diagnosed with recurrent exertional rhabdomyolysis (RER) and 7 clinically normal adult Thoroughbred or mixed-breed horses as control subjects.
- Their experiment focused on measuring variables related to muscle contraction, specifically twitch time course variables and contracture responses to various concentrations of chemical substances like potassium, caffeine, and halothane. These measurements were done on small bundles of intact external intercostal muscle cells from both clinically normal horses and those with RER.
Results of the study
- The study found that the threshold for significant muscle contracture induced by potassium depolarization (a process affecting the nerve cell’s electrical charge), is lower in RER-affected muscles than those in normal muscles.
- There was no difference in the relationship between potassium concentration and the change in membrane potential (the voltage difference) in both normal and RER-affected muscles.
- In contrast to control muscles, RER-affected muscles demonstrated lowered thresholds of contracture when exposed to caffeine and halothane. This implies a probable defect in the regulation of myoplasmic calcium, a significant element in muscle contraction and relaxation.
Conclusion and implications of the study
- Overall, the research discovered that Thoroughbreds with RER have an abnormal regulation of muscle contraction, possibly due to an issue with intracellular calcium regulation.
- This insight into the specific defect may lead to improved prevention and treatment strategies for the disorder in horses.
Cite This Article
APA
Lentz LR, Valberg SJ, Balog EM, Mickelson JR, Gallant EM.
(1999).
Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis.
Am J Vet Res, 60(8), 992-999.
Publication
Researcher Affiliations
- Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108.
MeSH Terms
- Anesthetics, Inhalation / pharmacology
- Animals
- Biopsy / veterinary
- Caffeine / pharmacology
- Central Nervous System Stimulants / pharmacology
- Female
- Halothane / pharmacology
- Horse Diseases / genetics
- Horse Diseases / physiopathology
- Horses
- Male
- Malignant Hyperthermia / physiopathology
- Malignant Hyperthermia / veterinary
- Membrane Potentials / physiology
- Muscle Contraction / genetics
- Muscle Contraction / physiology
- Muscle, Skeletal / physiopathology
- Pedigree
- Physical Exertion / physiology
- Potassium / physiology
- Recurrence
- Regression Analysis
- Rhabdomyolysis / genetics
- Rhabdomyolysis / physiopathology
- Rhabdomyolysis / veterinary
Grant Funding
- AR41270 / NIAMS NIH HHS
Citations
This article has been cited 8 times.- Autry JM, Svensson B, Carlson SF, Chen Z, Cornea RL, Thomas DD, Valberg SJ. Sarcoplasmic Reticulum from Horse Gluteal Muscle Is Poised for Enhanced Calcium Transport. Vet Sci 2021 Nov 23;8(12).
- Aldrich K, Velez-Irizarry D, Fenger C, Schott M, Valberg SJ. Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses. PLoS One 2021;16(2):e0244556.
- Autry JM, Karim CB, Perumbakkam S, Finno CJ, McKenzie EC, Thomas DD, Valberg SJ. Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle. Vet Sci 2020 Nov 13;7(4).
- Breed D, Meyer LCR, Steyl JCA, Goddard A, Burroughs R, Kohn TA. Conserving wildlife in a changing world: Understanding capture myopathy-a malignant outcome of stress during capture and translocation. Conserv Physiol 2019;7(1):coz027.
- Valberg SJ, Soave K, Williams ZJ, Perumbakkam S, Schott M, Finno CJ, Petersen JL, Fenger C, Autry JM, Thomas DD. Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis. J Vet Intern Med 2019 Mar;33(2):933-941.
- Norton EM, Mickelson JR, Binns MM, Blott SC, Caputo P, Isgren CM, McCoy AM, Moore A, Piercy RJ, Swinburne JE, Vaudin M, McCue ME. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data. J Hered 2016 Nov;107(6):537-43.
- Fritz KL, McCue ME, Valberg SJ, Rendahl AK, Mickelson JR. Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds. Anim Genet 2012 Dec;43(6):730-8.
- Isgren CM, Upjohn MM, Fernandez-Fuente M, Massey C, Pollott G, Verheyen KL, Piercy RJ. Epidemiology of exertional rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance. PLoS One 2010 Jul 14;5(7):e11594.
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