The Malignant Hyperthermia G2435r Mutation Causes Constitutive Ryr1 Openings

Many single-point mutations of the skeletal Ca2+-release ryanodine receptor (RyR1) channel are associated with malignant hyperthermia (MH) a potentially fatal disorder. MH can be triggered by volatile anaesthetics and suxamethonium, causing high temperatures and uncontrolled release of skeletal muscle SR Ca2+. The G2435R mutation is the most common mutation associated with human MH in the UK, however, the resulting changes to RyR1 ion-channel function are not known. We have therefore compared the single-channel properties of native RyR1 obtained from wild type (WT) or G2435R mutant mouse skeletal muscle after incorporation into artificial membranes under voltage-clamp conditions.