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 receptors and a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
found primarily in
skeletal muscle. In humans, it is encoded by the ''RYR1''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
RYR1 functions as a
calcium
Calcium is a chemical element with the 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 t ...
release channel in the
sarcoplasmic reticulum
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...
, 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
Central core disease (CCD), also known as central core myopathy, is an autosomal dominantly inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is charact ...
, minicore myopathy with external
ophthalmoplegia
Ophthalmoparesis refers to weakness (-paresis) or paralysis (-plegia) of one or more extraocular muscles which are responsible for eye movements. It is a physical finding in certain neurologic, ophthalmologic, and endocrine disease.
Internal ...
and
samaritan myopathy, a benign congenital myopathy.
Alternatively spliced transcripts encoding different isoforms have been demonstrated.
Dantrolene
Dantrolene sodium, sold under the brand name Dantrium among others, is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum s ...
may be the only known drug that is effective during cases of malignant hyperthermia.
Interactions
RYR1 has been shown to
interact with:
*
calmodulin
*
FKBP1A
*
HOMER1
Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the ''HOMER1'' gene. Other names are Vesl and PSD-Zip45.
Structure
Homer1 protein has an N-terminal EVH1 domain, involved in protein interaction, and a C-te ...
[
* HOMER2][ and
* TRDN.]
See also
* Ryanodine receptor
References
Further reading
*
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