typically associated with malfunctions in the Ryanodine receptor, malignant hypothermia is especially a risk for patients with genetic disorders in the receptor and who take halogenated hydrocarbon inhaled anesthetics.
malignant hypothermia is the unopposed consumption of ATP in muscles with excessive oxygen consumption. Ryanodine receptor is used as a bridge to communicate T-tubule depolarization to the sarcoplasmic reticulum, which has stored Ca++. depolarization triggers Ryanodine receptor to release stored Ca++, leading to cross-bridge cycling in the muscle cell and contraction.
in malignant hyperthermia, these receptors are defective and release excessive Ca++. the real kicker is that the excess Ca++ released needs to be reabsorbed – this requires alot of ATP. excess mitochondrial oxidative phosphorylation cycles occur to generate this, leading to heat generation (hyperthermia).
halogenated hydrocarbons bind to the Ryanodine receptor defect and expose this weakness. drugs that trigger this include:
- halothane
- isoflurane
- sevoflurane
- succinycholine (an exception, as it is not halogenated)
the antidote is dantrolene. this molecule binds to Ryanodine receptor and deactivates it.
