Ryanodine receptor 1

Ryanodine receptor 1 (RYR1) is a protein that in humans is encoded by the RYR1 gene. It is one of the ryanodine receptors, which are calcium channels in the sarcoplasmic reticulum of skeletal muscle cells. Mutations in the RYR1 gene are associated with several disorders, including malignant hyperthermia, central core disease, and multiminicore disease.

Structure

The RYR1 protein is a large homotetramer with a molecular mass of approximately 565 kDa per subunit. It is composed of a large cytoplasmic domain and a smaller transmembrane domain. The cytoplasmic domain contains the binding sites for ryanodine and dihydropyridine, while the transmembrane domain forms the calcium channel.

Function

RYR1 is primarily found in skeletal muscle, where it plays a key role in excitation-contraction coupling. Upon depolarization of the muscle cell, the dihydropyridine receptor (a voltage-gated calcium channel) in the T-tubule membrane mechanically interacts with RYR1, causing it to open and release calcium ions from the sarcoplasmic reticulum into the cytosol. This increase in cytosolic calcium concentration triggers muscle contraction.

Clinical significance

Mutations in the RYR1 gene can lead to a variety of muscle disorders. Malignant hyperthermia is a potentially fatal reaction to certain anesthetics, characterized by a rapid increase in body temperature and severe muscle contractions. Central core disease and multiminicore disease are congenital myopathies that cause muscle weakness and hypotonia. In addition, some mutations in RYR1 have been associated with King-Denborough syndrome, a rare disorder characterized by distinctive facial features, skeletal abnormalities, and susceptibility to malignant hyperthermia.

See also

• Ryanodine receptor
• Malignant hyperthermia
• Central core disease
• Multiminicore disease