Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is one of a class of

ryanodine receptor Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissu ...

s and a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

found primarily in

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

. In humans, it is encoded by the ''RYR1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

RYR1 functions as a

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule. RYR1 is associated with the dihydropyridine receptor (L-type calcium channels) within the sarcolemma of the T-tubule, which opens in response to depolarization, and thus effectively means that the RYR1 channel opens in response to depolarization of the cell. RYR1 plays a signaling role during embryonic skeletal myogenesis. A correlation exists between RYR1-mediated Ca2+ signaling and the expression of multiple molecules involved in key myogenic signaling pathways. Of these, more than 10 differentially expressed genes belong to the Wnt family which are essential for differentiation. This coincides with the observation that without RYR1 present, muscle cells appear in smaller groups, are underdeveloped, and lack organization. Fiber type composition is also affected, with less type 1 muscle fibers when there are decreased amounts of RYR1. These findings demonstrate RYR1 has a non-contractile role during muscle development. RYR1 is mechanically linked to neuromuscular junctions for the calcium release-calcium induced biological process. While nerve-derived signals are required for acetylcholine receptor cluster distribution, there is evidence to suggest RYR1 activity is an important mediator in the formation and patterning of these receptors during embryological development. The signals from the nerve and RYR1 activity appear to counterbalance each other. When RYR1 is eliminated, the acetylcholine receptor clusters appear in an abnormally narrow pattern, yet without signals from the nerve, the clusters are scattered and broad. Although their direct role is still unknown, RYR1 is required for proper distribution of acetylcholine receptor clusters.

Clinical significance

Mutations in the ''RYR1'' gene are associated with

malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...

susceptibility, central core disease, minicore myopathy with external ophthalmoplegia and

samaritan Samaritans (; ; ; ), are an ethnoreligious group originating from the Hebrews and Israelites of the ancient Near East. They are indigenous to Samaria, a historical region of History of ancient Israel and Judah, ancient Israel and Judah that ...

myopathy, a benign congenital myopathy. Alternatively spliced transcripts encoding different isoforms have been demonstrated. Dantrolene may be the only known drug that is effective during cases of malignant hyperthermia.

Interactions

RYR1 has been shown to interact with: *

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all Eukaryote, eukaryotic cells. It is an intracellular target of the Second messenger system, sec ...

* FKBP1A * HOMER1 * HOMER2 * HOMER3 and * TRDN.

References

External links

*
GeneReviews/NIH/UW entry on Multiminicore Disease

GeneReviews/NCBI/NIH/UW entry on Malignant Hyperthermia Susceptibility

RYR1 Variation Database
{{DEFAULTSORT:Ryr1 Ion channels Muscle stabilizers

Function

Clinical significance

Interactions

See also

References

Further reading

External links