What is the mechanism behind the increased temperature in malignant hyperthermia?

• A. Excessive use of ATP to sequester the calcium that was released
• B. Increased heat production from uncoupled oxidative phosphorylation
• C. Decreased ATP production due to mitochondrial failure
• D. Increased peripheral vasodilation causing heat loss

Answer: (A)

Malignant hyperthermia causes a surge of calcium release from the sarcoplasmic reticulum in skeletal muscle. That calcium triggers continuous muscle contraction, and restoring calcium to its storage requires a lot of ATP. The ATP is used by the Ca2+-ATPase pumps to resequester calcium and by the contractile machinery (myosin ATPase) to sustain contraction. This enormous ATP hydrolysis produces a lot of heat, driving the marked hyperthermia. Other ideas don’t fit the mechanism: heat from uncoupled oxidative phosphorylation isn’t the primary driver here, ATP production isn’t decreased but taxed by excessive demand, and vasodilation would promote heat loss rather than heat gain.