Calcium regulation by skeletal muscle membranes of horses with recurrent exertional rhabdomyolysis.
OBJECTIVE
To determine whether an alteration in calcium regulation by skeletal muscle sarcoplasmic reticulum, similar to known defects that cause malignant hyperthermia (MH), could be identified in membrane vesicles isolated from the muscles of Thoroughbreds with recurrent exertional rhabdomyolysis (RER).


METHODS
Muscle biopsy specimens from 6 Thoroughbreds with RER and 6 healthy (control) horses.


METHODS
RER was diagnosed on the basis of a history of > 3 episodes of exertional rhabdomyolysis confirmed by increases in serum creatine kinase (CK) activity. Skeletal muscle membrane vesicles, prepared by differential centrifugation of muscle tissue homogenates obtained from the horses, were characterized for sarcoplasmic reticulum (SR) activities, including the Ca2+ release rate for the ryanodine receptor-Ca2+ release channel, [3H]ryanodine binding activities, and rate of SR Ca2+-ATPase activity and its activation by Ca2+.


RESULTS
Time course of SR Ca2+-induced Ca2+ release and [3H]ryanodine binding to the ryanodine receptor after incubation with varying concentrations of ryanodine, caffeine, and ionized calcium did not differ between muscle membranes obtained from control and RER horses. Furthermore, the maximal rate of SR Ca2+-ATPase activity and its affinity for Ca2+ did not differ between muscle membranes from control horses and horses with RER.


CONCLUSIONS
Despite clinical and physiologic similarities between RER and MH, we concluded that RER in Thoroughbreds does not resemble the SR ryanodine receptor defect responsible for MH and may represent a novel defect in muscle excitation-contraction coupling, calcium regulation, or contractility.
Ward
T L
TL
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St. Paul 55108, USA.
Valberg
S J
SJ
Gallant
E M
EM
Mickelson
J R
JR
D000818:Animals; D001706:Biopsy / Q000662:veterinary; D002110:Caffeine / Q000737:chemistry; D002118:Calcium / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006734:Horse Diseases / Q000209:etiology / Q000503:physiopathology*; D006736:Horses; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology*; D005082:Physical Exertion; D012008:Recurrence; D012206:Rhabdomyolysis / Q000209:etiology / Q000503:physiopathology / Q000662:veterinary*; D012433:Ryanodine / Q000737:chemistry; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012588:Scintillation Counting / Q000662:veterinary
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D000252:Calcium-Transporting ATPases; D002118:Calcium