A 22-year-old man undergoes emergency surgery under halothane anesthesia with succinylcholine induction. Twenty minutes later he develops generalized muscle rigidity, tachycardia, mixed respiratory and metabolic acidosis, and a temperature of 41 degrees Celsius. The defect responsible lies in which protein?

• A Postsynaptic nicotinic acetylcholine receptor
• B Presynaptic voltage-gated calcium channel
• C Ryanodine receptor (RyR1) of the skeletal muscle sarcoplasmic reticulum ✓
• D Sarcoplasmic reticulum SERCA pump

Explanation

Malignant hyperthermia is most commonly caused by autosomal dominant mutations in RyR1. Volatile anesthetics and succinylcholine trigger uncontrolled, sustained calcium release from the terminal cisternae, producing continuous cross-bridge cycling, rigidity, massive heat generation, and rhabdomyolysis. Treatment is dantrolene, which blocks the RyR1 channel. C presynaptic calcium channel defect describes Lambert-Eaton syndrome, and a postsynaptic receptor defect describes myasthenia gravis, neither of which produces rigidity or hyperthermia.

Reference: Ganong's Review of Medical Physiology, 26th ed.

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Written and medically reviewed by the StethoPrep medical team.