CommentariesRegulation of ryanodine receptors by reactive nitrogen species
Section snippets
RyRs
RyRs are calcium channels that control the levels of intracellular Ca2+ by releasing Ca2+ from intracellular calcium-storing organelles 6, 7, 8. They were named RyRs because of the specific binding of the plant alkaloid ryanodine, which has facilitated their purification and characterization. Mammalian tissues express three structurally and functionally related RyRs (RyR1, RyR2, and RyR3) that are encoded by three different genes. RyR1, RyR2, and RyR3 are also known as skeletal, cardiac, and
NOSs
NO is derived from one of the chemically equivalent guanidino nitrogens of l-arginine in a reaction catalyzed by one of three NOSs [19]. nNOS (NOS-1), first identified in neurons, and eNOS (NOS-3), first identified in endothelial cells, are most often constitutively expressed 2, 3. They are activated by extracellular signals that increase intracellular [Ca2+] and thereby facilitate the interaction of the two enzymes with calmodulin. More recent evidence suggests that they can be also activated
Localization of NOSs and RyRs in striated muscle
Regulation of RyRs by NO (or related molecules) does not require that NOS and RyR co-localize, nor must they be expressed in the same cell. After all, NO, initially identified as the endothelial derived relaxation factor, has been shown to diffuse from endothelial cells to vascular smooth muscle cells to cause vasorelaxation [27]. Nevertheless, a close proximity of the two proteins could be advantageous in that it should restrict NO signaling to specific targets within a limited
Regulation of RyR by NO via cGMP-dependent pathways
NO increases cGMP levels in muscle, and such increases may alter RyR activities 1, 2, 3. One possible mechanism may involve phosphorylation of RyRs by cGMP-dependent protein kinase [44]. cGMP also may indirectly control RyRs by changing the cytosolic levels of RyR effectors such as cADP-ribose. In sea urchin eggs, NO increased the levels of the RyR activator cADP-ribose via a cGMP-dependent mechanism [45]. Treatment of a pheochromocytoma cell line, PC12, with NO donors led to a modest increase
Regulation of L-type Ca2+ channels by NO
In striated muscle, RyRs are regulated by L-type Ca2+ channels via either a direct physical interaction (in skeletal muscle) or an influx of extracellular Ca2+ (in cardiac muscle) 6, 7, 8. NO therefore also may modulate the release of Ca2+ from the SR by interacting with L-type Ca2+ channels via cGMP-dependent and independent pathways. Wang et al.[26] have suggested a cGMP-mediated regulation of L-type Ca2+ channels in cat atrial myocytes. Campbell et al.[24] studied the effects of NO-related
Concluding remarks
Although recent progress has led to an improved understanding of the interaction of NO and related species with RyRs, several major questions regarding their action on SR Ca2+ release remain to be resolved:
- 1.
Is NO a direct physiological modulator of RyRs in striated muscle? The cardiac RyR is endogenously S-nitrosylated [18]; however, the extent of S-nitrosylation was low and the physiological significance of this reaction (inhibitory or stimulatory) remains to be better established.
- 2.
Do RyRs and
Acknowledgements
Support by United States Public Health Service Grants HL52529 and HL59130 (to J.J.S.) and AR18687 and HL27430 (to G.M.) is gratefully acknowledged.
References (62)
Redox signalling, nitrosylation and related target interactions of nitric oxide
Cell
(1994)- et al.
Sulfhydryl oxidation induces rapid calcium release from sarcoplasmic reticulum vesicles
J Biol Chem
(1986) - et al.
Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide
FEBS Lett
(1996) - et al.
Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide
Cell Calcium
(1997) - et al.
Glutathione modulates ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Evidence for redox regulation of the Ca2+ release mechanism
J Biol Chem
(1997) - et al.
Nitric oxide activates skeletal and cardiac ryanodine receptors
Cell Calcium
(1997) - et al.
Nitric oxide protects the skeletal muscle Ca2+ release channel from oxidation induced activation
J Biol Chem
(1997) - et al.
Measurement of nitric oxide and peroxynitrite generation in the postischemic heart
J Biol Chem
(1996) Role of nitric oxide and its intracellular signalling pathways in the control of Ca2+ homeostasis
Biochem Pharmacol
(1998)- et al.
Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy
Cell
(1995)
Localization of nitric oxide synthase in human skeletal muscle
Biochem Biophys Res Commun
Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and α1-syntrophin mediated by PDZ domains
Cell
Communication-interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle
J Biol Chem
Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins
J Biol Chem
Endothelial type nitric oxide synthase in skeletal muscle fibers: Mitochondrial relationships
Biochem Biophys Res Commun
Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes
J Biol Chem
Nitric oxide induces intracellular Ca2+ mobilization and increases secretion of incorporated 5-hydroxytryptamine in rat pancreatic cells
FEBS Lett
Phosphorylation of serine 2843 in ryanodine receptor-calcium release channel of skeletal muscle by cAMP-, cGMP- and CaM-dependent protein kinase
Biochim Biophys Acta
Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway
J Biol Chem
The type 2 ryanodine receptor of neurosecretory PC12 cells is activated by cyclic ADP-ribose
J Biol Chem
Molecular interaction between ryanodine receptor and glycoprotein triadin involves redox cycling of functionally important hyperreactive sulfhydryls
J Biol Chem
Hydrogen peroxide stimulates the Ca2+ release channel from skeletal muscle sarcoplasmic reticulum
J Biol Chem
Sulfhydryl oxidation modifies the calcium dependence of ryanodine-sensitive calcium channels of excitable cells
Biophys J
Reactive disulfide compounds induce Ca2+ release from cardiac sarcoplasmic reticulum
Arch Biochem Biophys
Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum
J Biol Chem
FK506 binding protein associated with the calcium release channel (ryanodine receptor)
J Biol Chem
A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor
J Biol Chem
Nitric oxide in skeletal muscle
Nature
Nitric oxide and cardiac function
Circ Res
Role of nitric oxide in skeletal muscle: Synthesis, distribution and functional importance
Acta Physiol Scand
Frequency-dependent activation of a constitutive nitric oxide synthase and regulation of contractile function in adult rat ventricular myocytes
Circ Res
Cited by (78)
Ryanodine Receptor Channelopathies in Skeletal and Cardiac Muscle
2016, Ion Channels in Health and DiseasePalmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca<sup>2+</sup> leak in cardiomyocytes: Role of adenine nucleotide translocase
2015, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Meaning that a low level of RyR2 S-nitrosylation per se does not affect significantly RyR2 function. On the other hand, oxidation of > 7 thiols per subunit induces an irreversible activation of the channel through disulfide bonds formation between RyR2 subunits [42–44]. Irreversible RyR2 oxidation unambiguously increases RyR2 open probability and SR Ca2 + leak, however the level of RyR2 S-nitrosylation, which is reversible, has been proposed to increase or decrease RyR2 open probability (for review see [45,46]).
Cytosolic calcium regulation in rat afferent vagal neurons during anoxia
2013, Cell CalciumCitation Excerpt :ROS derive mainly from mitochondria or NADPH oxidase, activating the ryanodine receptor [52,54]. Alternatively NO production has also been reported to increase in hypoxia in these neurons which could also activate ryanodine receptors [13,55,56]. However, the production of either NO or ROS in anoxia seems unlikely since both require molecular oxygen as a substrate.
Hypoxia-induced changes in pulmonary and systemic vascular resistance: Where is the O<inf>2</inf> sensor?
2010, Respiratory Physiology and NeurobiologyInteractions between calcium and reactive oxygen species in pulmonary arterial smooth muscle responses to hypoxia
2010, Respiratory Physiology and Neurobiology