Calcium regulation by skeletal muscle membranes of horses with recurrent exertional rhabdomyolysis.

The research studied calcium regulation in the muscles of Thoroughbred horses suffering from recurrent exertional rhabdomyolysis (RER), a muscle disorder, and found no similarities with a known calcium regulation defect associated with a condition called malignant hyperthermia (MH).

Objective of the Study

• The main objective of the research was to explore whether a modification in calcium regulation by the muscle sarcoplasmic reticulum (a major organelle found in muscle cells), mirroring known defects that lead to malignant hyperthermia (MH) in humans, could be identified in membrane vesicles taken from the muscles of Thoroughbreds with recurring exertional rhabdomyolysis (RER).

Methodology

• For this study, muscle biopsy specimens from 6 Thoroughbreds diagnosed with RER and 6 healthy horses were used.
• RER diagnosis was based on a history of more than 3 episodes of exertional rhabdomyolysis, confirmed by rises in serum creatine kinase activity, an enzyme that indicates muscle damage.
• Skeletal muscle membrane vesicles were prepared by differential centrifugation of muscle tissue homogenates acquired from the horses, and various activities of these vesicles, particularly concerning calcium, were studied.

Results

• Results showed that the time course of calcium-induced calcium release and the binding of a radioactive compound (3H ryanodine) to the ryanodine receptor after incubation with varying concentrations of substances that influence muscle contraction and calcium levels, did not vary between membranes obtained from healthy and RER horses.
• Moreover, the maximal rate of SR Ca2+-ATPase activity, an important enzyme for transporting calcium into the sarcoplasmic reticulum, and its affinity for Calcium did not change between muscle membranes from healthy and RER horses.

Conclusions

• The study concluded that despite the clinical and physiological similarities between RER and MH, RER in Thoroughbreds does not resemble the sarcoplasmic reticulum ryanodine receptor defect responsible for malignant hyperthermia.
• This suggests that RER may be a distinct defect in muscle excitation-contraction coupling, calcium regulation, or contractility.