Point mutation in the calcium release channel of the sarcoplasmic reticulum (ryanodine receptor, RYR) gene have been demonstrated in some extended families as well as all MH (or porcine stress syndrome [PSS])-susceptible swine. This mutation/defect allows excessive release of calcium from the sarcoplasmic reticulum. The sustained massive increase in sarcoplasmic calcium level overwhelms the capacity of the muscle cell for active calcium reuptake to maintain the resting calcium level. The resultant excess intracellular calcium causes the the clinical features observed in MH—muscle rigidity, hypermetabolic state, muscle damage, and severe electrolyte and acid–base imbalances. The ability of the sarcoplasmic reticulum to re-sequester calcium appears normal when examined in vitro without the triggering agents (volatile anesthetics and succinylcholine) (12).

This mutation is heritable but with variable expression or penetrance. Although present in some families with MH, this mutation in RYR1 is absent in other cases of MH, pointing to other genes or mechanisms that may also be involved.