A 22-year-old man undergoing general anaesthesia with halothane and succinylcholine develops rapid onset of hyperthermia, masseter rigidity, and a steep rise in end-tidal carbon dioxide. The defect lies in which protein?

• A Ryanodine receptor of the sarcoplasmic reticulum ✓
• B Dihydropyridine receptor of the T-tubule
• C Sarcoplasmic reticulum calcium ATPase (SERCA)
• D Voltage-gated sodium channel of the sarcolemma

Explanation

Malignant hyperthermia is an autosomal dominant disorder most often caused by mutations in RyR1, the sarcoplasmic reticulum calcium release channel. Halothane and succinylcholine trigger uncontrolled channel opening, sustained cytosolic calcium elevation, continuous cross-bridge cycling, and massive heat and CO2 generation. The DHPR may be involved in rare families, but RyR1 accounts for the large majority. Treatment is dantrolene, which blocks this same release channel.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.