scholarly journals Crystal Structures of the N-Terminal Domains of Cardiac and Skeletal Muscle Ryanodine Receptors: Insights into Disease Mutations

Structure ◽  
2009 ◽  
Vol 17 (11) ◽  
pp. 1505-1514 ◽  
Author(s):  
Paolo Antonio Lobo ◽  
Filip Van Petegem
Keyword(s):  
Skeletal Muscle ◽  
Crystal Structures ◽  
Ryanodine Receptors ◽  
Disease Mutations ◽  
Terminal Domains

scholarly journals Cross talk between Ca 2+ and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca 2+ release channels

2005 ◽  
Vol 360 (1464) ◽  
pp. 2237-2246 ◽  
Author(s):  
Cecilia Hidalgo
Keyword(s):  
Skeletal Muscle ◽  
Neuronal Plasticity ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Nitrogen Species ◽  
Redox Modulation ◽  
Redox Active ◽  
Signalling Cascades ◽  
Sequential Activation ◽  
Redox Molecules

Calcium release mediated by the ryanodine receptors (RyR) Ca 2+ release channels is required for muscle contraction and contributes to neuronal plasticity. In particular, Ca 2+ activation of RyR-mediated Ca 2+ release can amplify and propagate Ca 2+ signals initially generated by Ca 2+ entry into cells. Redox modulation of RyR function by a variety of non-physiological or endogenous redox molecules has been reported. The effects of RyR redox modification on Ca 2+ release in skeletal muscle as well as the activation of signalling cascades and transcription factors in neurons will be reviewed here. Specifically, the different effects of S -nitrosylation or S -glutathionylation of RyR cysteines by endogenous redox-active agents on the properties of skeletal muscle RyRs will be discussed. Results will be presented indicating that these cysteine modifications change the activity of skeletal muscle RyRs, modify their behaviour towards both activators and inhibitors and affect their interactions with FKBP12 and calmodulin. In the hippocampus, sequential activation of ERK1/2 and CREB is a requisite for Ca 2+ -dependent gene expression associated with long-lasting synaptic plasticity. The effects of reactive oxygen/nitrogen species on RyR channels from neurons and RyR-mediated sequential activation of neuronal ERK1/2 and CREB produced by hydrogen peroxide and other stimuli will be discussed as well.

Characterization of RyR1-slow, a ryanodine receptor specific to slow-twitch skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. R1889-R1898 ◽  
Author(s):  
Jeffery Morrissette ◽  
Le Xu ◽  
Alexandra Nelson ◽  
Gerhard Meissner ◽  
Barbara A. Block
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Fiber Type ◽  
Ryanodine Receptors ◽  
Open Probability ◽  
Dependent Inhibition ◽  
Single Channel Activity ◽  
Intracellular Ca ◽  
Slow Twitch ◽  
Fast Twitch

Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type–specific manner in fish skeletal muscle (11). In this study, we compare [3H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [3H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (Po) of RyR1-slow was threefold less than the maximum Po of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest Po of all the RyR channels and displayed less inhibition at millimolar Ca2+. The addition of 5 mM Mg-ATP or 2.5 mM β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP) to the channels increased the Po and [3H]ryanodine binding of both RyR1s but also caused a shift in the Ca2+ dependency curve of RyR1-slow such that Ca2+-dependent inactivation was attenuated. [3H]ryanodine binding data also showed that Mg2+-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca2+ is regulated in these muscle types.

NF-κB activation by depolarization of skeletal muscle cells depends on ryanodine and IP3 receptor-mediated calcium signals

2007 ◽  
Vol 292 (5) ◽  
pp. C1960-C1970 ◽  
Author(s):  
Juan Antonio Valdés ◽  
Jorge Hidalgo ◽  
José Luis Galaz ◽  
Natalia Puentes ◽  
Mónica Silva ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Field Potential ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Ip3 Receptor ◽  
Pharmacological Agents ◽  
Calcium Dependent ◽  
Element Binding Protein

Depolarization of skeletal muscle cells by either high external K+ or repetitive extracellular field potential pulses induces calcium release from internal stores. The two components of this release are mediated by either ryanodine receptors or inositol 1,4,5-trisphosphate (IP3) receptors and show differences in kinetics, amplitude, and subcellular localization. We have reported that the transcriptional regulators including ERKs, cAMP/Ca2+-response element binding protein, c- fos, c- jun, and egr-1 are activated by K+-induced depolarization and that their activation requires IP3-dependent calcium release. We presently describe the activation of the nuclear transcription factor NF-κB in response to depolarization by either high K+ (chronic) or electrical pulses (fluctuating). Calcium transients of relative short duration activate an NF-κB reporter gene to an intermediate level, whereas long-lasting calcium increases obtained by prolonged electrical stimulation protocols of various frequencies induce maximal activation of NF-κB. This activation is independent of extracellular calcium, whereas calcium release mediated by either ryanodine or IP3 receptors contribute in all conditions tested. NF-κB activation is mediated by IκBα degradation and p65 translocation to the nucleus. Partial blockade by N-acetyl-l-cysteine, a general antioxidant, suggests the participation of reactive oxygen species. Calcium-dependent signaling pathways such as those linked to calcineurin and PKC also contribute to NF-κB activation by depolarization, as assessed by blockade through pharmacological agents. These results suggest that NF-κB activation in skeletal muscle cells is linked to membrane depolarization and depends on the duration of elevated intracellular calcium. It can be regulated by sequential activation of calcium release mediated by the ryanodine and by IP3 receptors.

Different interactions of cardiac and skeletal muscle ryanodine receptors with FK-506 binding protein isoforms

1997 ◽  
Vol 272 (5) ◽  
pp. C1726-C1733 ◽  
Author(s):  
S. Barg ◽  
J. A. Copello ◽  
S. Fleischer
Keyword(s):  
Skeletal Muscle ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Ryanodine Receptors ◽  
Protein Isoforms ◽  
Channel Activity ◽  
Functional Interaction ◽  
Fk 506 ◽  
Receptor Isoforms ◽  
Functional Consequences

In the present study, we compare functional consequences of dissociation and reconstitution of binding proteins FKBP12 and FKBP12.6 with ryanodine receptors from cardiac (RyR2) and skeletal muscle (RyR1). The skeletal muscle RyR1 channel became activated on removal of endogenously bound FKBP12, consistent with previous reports. Both FKBP12 and FKBP12.6 rebind to FKBP-depleted RyR1 and restore its quiescent channel behavior by altering ligand sensitivity, as studied by single-channel recordings in planar lipid bilayers, and macroscopic behavior of the channels (ryanodine binding and net energized Ca2- uptake). By contrast, removal of FKBP12.6 from the cardiac RyR2 did not modulate the function of the channel using the same types of assays as for RyR1. FKBP12 or FKBP12.6 had no effect on channel activity of FKBP12.6-depleted cardiac RyR2, although FKBP12.6 rebinds. Our studies reveal important differences between the two ryanodine receptor isoforms with respect to their functional interaction with FKBP12 and FKBP12.6.

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