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Mini Reviews in Medicinal Chemistry 2019Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They regulate the release of stored... (Review)
Review
Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They regulate the release of stored intracellular calcium and play a critical role in muscle contraction. The N-terminal part of these receptors accounts for roughly 80% and contains the binding sites for diverse RyRs modulators. The C-terminal domain contains the transmembrane region. This review summarizes the current knowledge about the molecular biology of insect RyRs, chemicals targeting mammal or insect RyRs, and the reasons for mammal RyR-related diseases and diamides resistances. It may lay the foundation for effective management of mammal RyR-related diseases and diamides resistances.
Topics: Animals; Diamide; Drug Discovery; Humans; Insect Control; Insecta; Insecticide Resistance; Insecticides; Ryanodine; Ryanodine Receptor Calcium Release Channel
PubMed: 29600763
DOI: 10.2174/1389557518666180330112908 -
Critical Reviews in Biochemistry and... 1994Recent findings on the ryanodine receptor of vertebrates, a Ca-release channel protein for the caffeine- and ryanodine-sensitive Ca pools, are reviewed in this article.... (Review)
Review
Recent findings on the ryanodine receptor of vertebrates, a Ca-release channel protein for the caffeine- and ryanodine-sensitive Ca pools, are reviewed in this article. Three distinct genes, i.e., ryr1, ryr2, and ryr3, express different isoforms in specific locations: Ryr1 in skeletal muscle and Purkinje cells of cerebellum; Ryr2 in cardiac muscle and brain, especially cerebellum; Ryr3 in skeletal muscle of nonmammalian vertebrates, the corpus striatum, and limbic cortex of brain, smooth muscles, and the other cells in vertebrates. While only one isoform (Ryr1) is expressed in mammalian skeletal muscles, two isoforms (alpha- and beta-isoforms expressed by ryr1 and ryr3, respectively) are found in nonmammalian vertebrate skeletal muscles. Although the coexistence of two isoforms may merely be related to differentiation and specialization, the biological significance remains to be clarified. Ryanodine receptors in vertebrate skeletal muscles are believed to mediate two different modes of Ca release: Ca(2+)-induced Ca release and action potential-induced Ca release. All results obtained so far with any isoform of ryanodine receptor are related to Ca(2+)-induced Ca release and show very similar characteristics. Ca(2+)-induced Ca release, however, cannot be the underlying mechanism of Ca release on skeletal muscle activation. Susceptibility of the ryanodine receptor's ryanodine-binding activity to modification by physical factors, such as osmolality of the medium, might be related to action potential-induced Ca release. A hypothesis of molecular interaction in view of the plunger model of action potential-induced Ca release is discussed, suggesting that the model could be compatible with Ryr1 and Ryr3, but incompatible with Ryr2. The functional relevance of ryanodine receptor isoforms, especially Ryr3, in brain also remains to be clarified. Among ryr1 gene-related diseases, malignant hyperthermia was the first to be identified; however, there is still the possibility of involvement of the other genes. Central core disease has been added to the list recently. A molecular approach for the diagnosis and treatment of diseases is now in progress.
Topics: Amino Acid Sequence; Animals; Brain; Calcium; Calcium Channels; Malignant Hyperthermia; Molecular Sequence Data; Muscle Proteins; Muscles; Myopathies, Nemaline; Ryanodine; Ryanodine Receptor Calcium Release Channel
PubMed: 8001396
DOI: 10.3109/10409239409083482 -
Frontiers in Immunology 2023Mast cell (MC) activation is implicated in the pathogenesis of multiple immunodysregulatory skin disorders. Activation of an IgE-independent pseudo-allergic route has...
Mast cell (MC) activation is implicated in the pathogenesis of multiple immunodysregulatory skin disorders. Activation of an IgE-independent pseudo-allergic route has been recently found to be mainly mediated Mas-Related G protein-coupled receptor X2 (MRGPRX2). Ryanodine receptor (RYR) regulates intracellular calcium liberation. Calcium mobilization is critical in the regulation of MC functional programs. However, the role of RYR in MRGPRX2-mediated pseudo-allergic skin reaction has not been fully addressed. To study the role of RYR , we established a murine skin pseudo-allergic reaction model. RYR inhibitor attenuated MRGPRX2 ligand substance P (SP)-induced vascular permeability and neutrophil recruitment. Then, we confirmed the role of RYR in an MC line (LAD2 cells) and primary human skin-derived MCs. In LAD2 cells, RYR inhibitor pretreatment dampened MC degranulation (detected by β-hexosaminidase retlease), calcium mobilization, IL-13, TNF-α, CCL-1, CCL-2 mRNA, and protein expression activated by MRGPRX2 ligands, namely, compound 48/80 (c48/80) and SP. Moreover, the inhibition effect of c48/80 by RYR inhibitor was verified in skin MCs. After the confirmation of RYR2 and RYR3 expression, the isoforms were silenced by siRNA-mediated knockdown. MRGPRX2-induced LAD2 cell exocytosis and cytokine generation were substantially inhibited by RYR3 knockdown, while RYR2 had less contribution. Collectively, our finding suggests that RYR activation contributes to MRGPRX2-triggered pseudo-allergic dermatitis, and provides a potential approach for MRGPRX2-mediated disorders.
Topics: Humans; Animals; Mice; Calcium; Ryanodine; Ryanodine Receptor Calcium Release Channel; Mast Cells; Receptors, G-Protein-Coupled; Dermatitis, Atopic; Nerve Tissue Proteins; Receptors, Neuropeptide
PubMed: 37404822
DOI: 10.3389/fimmu.2023.1207249 -
International Journal of Molecular... Jan 2001The properties of a ryanodine-sensitive Ca2+ release channel (receptor) in non-excitable cells like exocrine cells or epithelial cells are described in this review. The... (Review)
Review
The properties of a ryanodine-sensitive Ca2+ release channel (receptor) in non-excitable cells like exocrine cells or epithelial cells are described in this review. The ryanodine-sensitive Ca2+ release from the microsomal vesicles is activated by Ca2+, caffeine, ryanodine or cyclic ADP-ribose (cADPR) and is inhibited by ruthenium red or higher concentrations (> or =100 microM) of ryanodine. The properties are similar to those of excitable cells such as muscle cells or neuronal tissues. In some non-excitable cells, the Ca2+ release induced by caffeine, ryanodine or cADPR is stimulated by calmodulin (CaM) or FK506. Kd values of [3H]ryanodine binding to the receptor protein range from 6 to 17 nM and are similar to those of a high-affinity binding site in skeletal or cardiac muscle. Maximum binding capacities (Bmax) range from 40 to 620 fmol/ mg protein and are 10 approximately 200-fold lower than those for a high-affinity binding site in skeletal muscle. Caffeine, adenine nucleotide AMP-PCP, Mg2+, ruthenium red or FK506 affects the binding. In some non-excitable cells, the ryanodine receptor (RyR) isoform RyR2 or RyR3 is expressed and has been identified. However, unlike for excitable cells, information concerning the RyR proteins, including binding sites for modulators like CaM and phosphorylation sites has not yet been obtained.
Topics: Animals; Calcium; Epithelial Cells; Exocrine Glands; Humans; Ryanodine; Ryanodine Receptor Calcium Release Channel
PubMed: 11115603
DOI: No ID Found -
Invertebrate Neuroscience : IN Sep 2008Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the... (Review)
Review
Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the sarcoplasmic reticulum of muscle and the endoplasmic reticulum of neurons and many other cell types. Ryanodine, a plant alkaloid and an important ligand used to characterize and purify the receptor, has served as a natural botanical insecticide, but attempts to generate synthetic commercial analogues of ryanodine have proved unsuccessful. Recently two classes of synthetic chemicals have emerged resulting in commercial insecticides that target insect RyRs. The phthalic acid diamide class has yielded flubendiamide, the first synthetic ryanodine receptor insecticide to be commercialized. Shortly after the discovery of the phthalic diamides, the anthranilic diamides were discovered. This class has produced the insecticides Rynaxypyr and Cyazypyr. Here we review the structure and functions of insect RyRs and address the modes of action of phthalic acid diamides and anthranilic diamides on insect ryanodine receptors. Particularly intersting is the inherent selectivity both chemical classes exhibit for insect RyRs over their mammalian counterparts. The future prospects for RyRs as a commercially-validated target site for insect control chemicals are also considered.
Topics: Animals; Benzamides; Calcium Signaling; Insect Proteins; Insecta; Insecticides; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sulfones; ortho-Aminobenzoates
PubMed: 18696132
DOI: 10.1007/s10158-008-0076-4 -
Pharmacological Reviews Mar 1997The goal of this review has been to describe the current state of the pharmacology of ryanodine and related compounds relative to the vertebrate RyRs. Resolution of... (Review)
Review
The goal of this review has been to describe the current state of the pharmacology of ryanodine and related compounds relative to the vertebrate RyRs. Resolution of questions concerning the molecular properties of RyR channel function and the contributions made by the RyR isoforms to cellular signaling in a variety of tissues will require the production of new pharmacological agents directed against these proteins. Novel naturally occurring ryanodine congeners have been identified, and significant advances have been made in developing chemical approaches that permit the structure of ryanodine to be derivatized in selective ways. Moreover, several of these changes have yielded compounds that differ in their binding affinities and in their abilities to modify the properties of the RyR channels. These advances give substance to the possibility of designing the required pharmacological agents based on rational design changes of the structure ryanodine.
Topics: Acylation; Alkylation; Animals; Calcium; Calcium Channels; Calmodulin-Binding Proteins; Humans; Models, Molecular; Muscle Proteins; Ryanodine; Ryanodine Receptor Calcium Release Channel; Structure-Activity Relationship; Vertebrates; Xenobiotics
PubMed: 9085309
DOI: No ID Found -
Biological Research 2004Ryanodine binds with high affinity and specificity to a class of Ca(2+)-release channels known as ryanodine receptors (RyR). The interaction with RyR results in a... (Review)
Review
Ryanodine binds with high affinity and specificity to a class of Ca(2+)-release channels known as ryanodine receptors (RyR). The interaction with RyR results in a dramatic alteration in function with open probability (Po) increasing markedly and rates of ion translocation modified. We have investigated the features of ryanodine that govern the interaction of the ligand with RyR and the mechanisms underlying the subsequent alterations in function by monitoring the effects of congeners and derivatives of ryanodine (ryanoids) on individual RyR2 channels. While the interaction of all tested ryanoids results in an increased Po, the amplitude of the modified conductance state depends upon the structure of the ryanoid. We propose that different rates of cation translocation observed in the various RyR-ryanoid complexes represent different conformations of the channel stabilized by specific conformers of the ligand. On the time scale of a single channel experiment ryanodine binds irreversibly to the channel. However, alterations in structure yield some ryanoids with dissociation rate constants orders of magnitude greater than ryanodine. The probability of occurrence of the RyR-ryanoid complex is sensitive to trans-membrane voltage, with the vast majority of the influence of potential arising from a voltage-driven alteration in the affinity of the ryanoid-binding site.
Topics: Animals; Biological Transport; Drug Interactions; Electric Conductivity; Membrane Potentials; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Structure-Activity Relationship
PubMed: 15709679
DOI: 10.4067/s0716-97602004000400006 -
Advances in Neurobiology 2023Ryanodine receptors (RyRs) are Ca release channels located in the endoplasmic reticulum membrane. Presynaptic RyRs play important roles in neurotransmitter release and...
Ryanodine receptors (RyRs) are Ca release channels located in the endoplasmic reticulum membrane. Presynaptic RyRs play important roles in neurotransmitter release and synaptic plasticity. Recent studies suggest that the proper function of presynaptic RyRs relies on several regulatory proteins, including aryl hydrocarbon receptor-interacting protein, calstabins, and presenilins. Dysfunctions of these regulatory proteins can greatly impact neurotransmitter release and synaptic plasticity by altering the function or expression of RyRs. This chapter aims to describe the interaction between these proteins and RyRs, elucidating their crucial role in regulating synaptic function.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Presenilins; Biological Transport; Neuronal Plasticity; Ryanodine; Neurotransmitter Agents
PubMed: 37615871
DOI: 10.1007/978-3-031-34229-5_11 -
Progress in Biophysics and Molecular... 2008To characterize the effects of inhibition of Ryanodine receptor (RyR), TTX-sensitive neuronal Na+ current (iNa), "rapidly activating" delayed rectifier K+ current (iKr)... (Review)
Review
AIMS
To characterize the effects of inhibition of Ryanodine receptor (RyR), TTX-sensitive neuronal Na+ current (iNa), "rapidly activating" delayed rectifier K+ current (iKr) and ultrarapid delayed rectifier potassium current (IKur) on the pacemaker activity of the sinoatrial node (SAN) and the atrioventricular node (AVN) in the mouse.
METHODS
The structure of mouse AVN was studied by histology and immunolabelling of Cx43 and hyperpolarization-activated, cyclic nucleotide-binding channels (HCN). The effects of Ryanodine, TTX, E-4031 and 4-AP on pacemaker activities recorded from mouse intact SAN and AVN preparations have been investigated.
RESULTS
Immuno-histological characterization delineated the structure of the AVN showing the similar molecular phenotype of the SAN. The effects of these inhibitors on the cycle length (CL) of the spontaneous pacemaker activity of the SAN and the AVN were characterized. Inhibition of RyR by 0.2 and 2 microM Ryanodine prolonged CL by 42+/-12.3% and 64+/-18.1% in SAN preparations by 163+/-72.3% and 241+/-91.2% in AVN preparations. Inhibition of TTX-sensitive iNa by 100 nM TTX prolonged CL by 22+/-6.0% in SAN preparations and 53+/-13.6% in the AVN preparations. Block of iKr by E-4031 prolonged CL by 68+/-12.5% in SAN preparations and 28+/-3.4% in AVN preparations. Inhibition of iKur by 50 microM 4-AP prolonged CL by 20+/-3.4% in SAN preparations and 18+/-3.0% in AVN preparations.
CONCLUSION
Mouse SAN and AVN showed distinct different response to the inhibition of RyR, TTX-sensitive INa, IKr and iKur, which reflects the variation in contribution of these currents to the pacemaker function of the cardiac nodes in the mouse. Our data provide valuable information for developing virtual tissue models of mouse SAN and AVN.
Topics: 4-Aminopyridine; Animals; Anti-Arrhythmia Agents; Atrioventricular Node; Mice; Piperidines; Potassium Channel Blockers; Pyridines; Ryanodine; Sinoatrial Node; Tetrodotoxin
PubMed: 17850852
DOI: 10.1016/j.pbiomolbio.2007.07.003 -
The Journal of General Physiology Aug 1990
Topics: Animals; Calcium; Calcium Channels; Muscles; Rabbits; Receptors, Cholinergic; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum
PubMed: 2170565
DOI: 10.1085/jgp.96.2.439