Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).
During exercise, defects in calcium (Ca2+) release have been proposed to impair muscle function. Here, we show that during exercise in mice and humans, the major Ca2+ release channel required for excitation-contraction coupling (ECC) in skeletal muscle, the ryanodine receptor (RyR1), is progressively PKA-hyperphosphorylated, S-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in "leaky" channels that cause decreased exercise tolerance in mice. Mice with skeletal muscle-specific calstabin1 deletion or PDE4D deficiency exhibited significantly impaired exercise capacity. A small molecule (S107) that prevents depletion of calstabin1 from the RyR1 complex improved force generation and exercise capacity, reduced Ca2+-dependent neutral protease calpain activity and plasma creatine kinase levels. Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity.
Catalysis of facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
Catalysis of the transmembrane transfer of a calcium ion by a channel that opens when a specific ligand has been bound by the channel complex or one of its constituent parts.
J. Biol. Chem. 272, 5256-5260 (1997)[PubMed:9030597]
Malignant hyperthermia is an inherited autosomal disorder of skeletal muscle in which certain volatile anesthetics and depolarizing muscle relaxants trigger an abnormally high release of Ca2+ from the intracellular Ca2+ store, the sarcoplasmic reticulum. In about 50% of cases, malignant hyperthermia susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor/Ca2+ release channel (RYR1). To date, eight point mutations have been identified in human RYR1. Although these mutations are thought to lead to an increased caffeine and halothane sensitivity in the contractile response of skeletal muscle, their functional consequences have not been investigated on the molecular level. In the present study, we provide the first functional characterization of a point mutation located in the central part of RYR1, Gly2434 --> Arg. Using high affinity [3H]ryanodine binding as the experimental approach, we show that this mutation enhances the sensitivity of RYR1 to activating concentrations of Ca2+ and to the exogenous and diagnostically used ligands caffeine and 4-chloro-m-cresol. In parallel, the sensitivity to inhibiting concentrations of Ca2+ and calmodulin was reduced, transferring the mutant Ca2+ release channel into a hyperexcitable state.
Interacting selectively and non-covalently with calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
Catalysis of the transmembrane transfer of a calcium ion by a channel that opens when a ryanodine class ligand has been bound by the channel complex or one of its constituent parts.
Ca(2+) mobilization from intracellular stores is mediated by Ca(2+) release channels, designated ryanodine and IP(3) receptors, and directly regulates important cellular reactions including muscle contraction, endo/exocrine secretion, and neural excitability. In order to function as an intracellular store, the endo/sarcoplasmic reticulum is equipped with cooperative Ca(2+) uptake, storage and release machineries, comprising synergic collaborations among integral-membrane, cytoplasmic and luminal proteins. Our recent studies have demonstrated that junctophilins form junctional membrane complexes between the plasma membrane and the endo/sarcoplasmic reticulum in excitable cells, and that TRIC (trimeric intracellular cation) channels act as novel monovalent cation-specific channels on intracellular membrane systems. Knockout mice have provided evidence that both junctophilins and TRIC channels support efficient ryanodine receptor-mediated Ca(2+) release in muscle cells. This review focuses on cardiac Ca(2+) release by discussing pathological defects of mutant cardiomyocytes lacking ryanodine receptors, junctophilins, or TRIC channels.
Catalysis of the transmembrane transfer of a calcium ion by a voltage-gated channel. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caffeine stimulus. Caffeine is an alkaloid found in numerous plant species, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.
Any process involved in the maintenance of an internal steady state of calcium ions within the cytosol of a cell or between the cytosol and its surroundings.
A process in which force is generated within muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis.
The formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone, involved in the progression of the skeleton from its formation to its mature state.
The process in which the anatomical structures of the outflow tract are generated and organized. The outflow tract is the portion of the heart through which blood flows into the arteries.
The process in which calcium ions sequestered in the endoplasmic reticulum, Golgi apparatus or mitochondria are released into the cytosolic compartment.
ISSOrtholog Curator
Release of sequestered calcium ion into cytosol by sarcoplasmic reticulumdefinition[GO:0014808]
The process in which the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol occurs via calcium release channels.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caffeine stimulus. Caffeine is an alkaloid found in numerous plant species, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
Hypoxia is a state of insufficient oxygen supply of the tissue or cell. Kidney tissue is highly sensitive to oxygen deprivation and easily develops renal ischemic injury. Calcium transporters very sensitively react to oxygen deficiency. We investigated whether hypoxia affects the gene expression of intracellular calcium transporters in the intact kidney, and we compared the response to that of HEK 293 cells. Our results showed that, while in mouse kidney tissue hypoxia elevates mRNA for inositol 1,4,5-trisphosphate receptors (IP3R) type 1 (IP3R1) and ryanodine receptors (RyR) type 2 (RyR2), in culture of HEK 293 cells the gene expression of all IP3Rs decreased without affecting viability of the cells. RyR2 mRNA in HEK 293 cells was not significantly changed, but RyR1 gene expression was significantly increased by hypoxia. The different response of kidney tissue and HEK 293 cells to hypoxia could be due to unequal differentiation state of the cells in intact tissue and cultured embryonic cell line. The physiological relevance of this observation remains to be determined.
The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast.
The process whose specific outcome is the progression of the skin over time, from its formation to the mature structure. The skin is the external membranous integument of an animal. In vertebrates the skin generally consists of two layers, an outer nonsensitive and nonvascular epidermis (cuticle or skarfskin) composed of cells which are constantly growing and multiplying in the deeper, and being thrown off in the superficial layers, as well as an inner vascular dermis (cutis, corium or true skin) composed mostly of connective tissue.
ISSOrtholog Curator
Pathways
According to KEGG, this protein belongs to the following pathways:
Protein involved in the transport of calcium ions. Calcium is essential for a variety of bodily functions, such as neurotransmission, muscle contraction and proper heart function.
Protein involved in the transport of ions. Such proteins are usually transmembrane and mediate a movement of ions across cell membranes. Transport may be passive (facilitated diffusion; down the electrochemical gradient), or active (against the electrochemical gradient). Active transport requires energy which may come from light, oxidation reactions, ATP hydrolysis, or cotransport of other ions or molecules.
Protein involved in the transport of a molecule (metabolite, protein, etc), a ion or an electron across cell membranes, inside the cell or in a tissue fluid.
Cell membrane glycoprotein forming a channel in a biological membrane selectively permeable to calcium ions. Calcium is essential for a variety of bodily functions, such as neurotransmission, muscle contraction and proper heart function.
Protein involved in development, the process whereby a multicellular organism develops from its early immature forms, e.g., zygote, larva, embryo, into an adult.
Protein which is part of a transmembrane protein complex that forms a hydrophilic channel across the lipid bilayer through which specific inorganic ions can diffuse down their electrochemical gradients. The channels are usually gated and only open in response to a specific stimulus, such as a change in membrane potential (voltage-gated) or the binding of a ligand (ligand-gated channel).
Protein which forms or is a component of a ligand-gated channel. Ligand-gated channels are transmembrane ion channels whose permeability is increased by the binding of a specific ligand, such as neurotransmitters, ionositol triphosphates, and cyclic nucleotides.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
My favorites 
My labels 
Login
