Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia

Liang, Xin; Chen, Keying; Fruen, Bradley R.; Hu, Jun; Ma, Jianjie; Hu, Xiaofang; Parness, Jerome

doi:10.1039/b907812f

Cited by 3 publications

(2 citation statements)

References 41 publications

(77 reference statements)

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“…Commonly used is a [ 3 H]ryanodine binding assay ( Figure 4C) [19,51,54,60,67,77,79,86,90,92,93,95,96,103,105,108,113,129] As opposed to whole-cell measurements, activities of a single channel can be recorded using planar lipid bilayer electrophysiology ( Figure 4D) [19, 53, 54, 67, 69, 77, 79, 99-101, 105, 107, 108, 111, 112, 114]. Recombinant or endogenous RyR from crude SR vesicle preparations or from purified material are fused into an artificial lipid bilayer formed across two chambers.…”

Section: Methodsmentioning

confidence: 99%

Structural Insights Into Disease Mutations of the Ryanodine Receptor

Yuchi¹,

Kimlicka²,

Petegem³

2013

Genetic Disorders

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Ca 2+ ions form important intracellular messenger molecules in nearly every cell type of the human body. Under so-called "resting" states of the cell, the concentration of Ca 2+ in the cytoplasm is extremely low (~10-7 M), but this can rapidly rise ~2 orders of magnitude when an appropriate signal is generated. Ca 2+ ions can enter the cytoplasm either from the extracellular space or from intracellular compartments, through specialized membrane proteins. These "calcium channels" are complex proteins, often consisting of multiple subunits, and are targets for multiple regulatory events. A major intracellular Ca 2+ store is the endoplasmic reticulum (ER), or its specialized form, the sarcoplasmic reticulum (SR) in muscle tissue. The mobilization of Ca 2+ from these organelles can trigger many Ca 2+-dependent events, such as the contraction of muscle tissue. The coupling between electrical excitation of a muscle cell and its subsequent contraction (excitation-contraction coupling, E-C coupling) is a finely orchestrated process that requires a functional cross-talk between proteins embedded in the plasma membrane and in the SR membrane (Figure 1). An electrical signal, a depolarization of the plasma membrane, can lead to opening of Ltype voltage-gated calcium channels (Ca V), which results in the influx of Ca 2+ into the cytoplasm. In the SR membrane, large calcium release channels called Ryanodine Receptors (RyRs) can detect this initial influx, and release more Ca 2+ in a process known as Ca 2+-induced Ca 2+ release (CICR). The latter event provides the bulk of the Ca 2+ required for contraction to occur. In this scenario, the RyRs form signal amplifiers, which both detect and augment the Ca 2+ signal [1, 2]. This scenario likely predominates in cardiac tissue, but Ca 2+ is not always required to open RyRs. In skeletal muscle, for example, various pieces of evidence suggest a direct interaction between the L-type calcium channel (Ca V 1.1) and the RyR [3-6]. In this case, the depolari

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Section: Methodsmentioning

confidence: 99%

Structural Insights Into Disease Mutations of the Ryanodine Receptor

Yuchi¹,

Kimlicka²,

Petegem³

2013

Genetic Disorders

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“…We used a well established porcine model of MH in which affected animals are homozygous for the RyR1 R615C mutation (Harrison et al, 1968). When this mutant form of RyR1 (RyR1 R615C ) was compared with the wild type RyR (RyR1 WT ), we found with both PCS and AFM that the purified RyR1 R615C showed significantly reduced oligomerization when compared to RyR1 WT (Liang et al, 2009). AFM observations showed that the number and size of RyR1 R615C clusters formed at a RyR1 concentration of 6 (g protein/mL at the closed state were significantly reduced (Fig.…”

Section: Introductionmentioning

confidence: 99%

High‐resolution imaging and nano‐manipulation of biological structures on surface

Zhang

Sun

et al. 2010

Microscopy Res & Technique

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In this mini-review we discuss our recent findings on imaging and manipulation of biological macromolecular structures by atomic force microscopy (AFM). In the first part of this review, we focus on high-resolution imaging of selected biological samples. AFM images of membrane proteins have revealed detailed conformational features related to identifiable biological functions. Different self-assembling behaviors of short peptides into supramolecular structures on various substrates under controlled environmental conditions have been systematically studied with AFM imaging. In the second part, we present a novel nano-manipulation technique for manipulating, isolating, amplifying, and sequencing of individual DNA molecules, which may find unique applications in the analysis of difficult sequence structures. Finally, we discuss how to characterize the elasticity of individual biomolecules and live cells. These results demonstrate that not only the high resolution capacity of the AFM is suited to resolve certain biological questions, but can also be applied to single molecule isolation and biomechanical analysis with its unique advantages.

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Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990–2019

Lawal

Wires

Terry

et al. 2020

Orphanet J Rare Dis

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Background Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics. Methods We conducted a comprehensive scoping review of scientific literature pertaining to RYR1-RM and MH preclinical model systems in accordance with the PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. Two major electronic databases (PubMed and EMBASE) were searched without language restriction for articles and abstracts published between January 1, 1990 and July 3, 2019. Results Our search yielded 5049 publications from which 262 were included in this review. A majority of variants tested in RYR1 preclinical models were localized to established MH/central core disease (MH/CCD) hot spots. A total of 250 unique RYR1 variations were reported in human/rodent/porcine models with 95% being missense substitutions. The most frequently reported RYR1 variant was R614C/R615C (human/porcine total n = 39), followed by Y523S/Y524S (rabbit/mouse total n = 30), I4898T/I4897T/I4895T (human/rabbit/mouse total n = 20), and R163C/R165C (human/mouse total n = 18). The dyspedic mouse was utilized by 47% of publications in the rodent category and its RyR1-null (1B5) myotubes were transfected in 23% of publications in the cellular model category. In studies of transfected HEK-293 cells, 57% of RYR1 variations affected the RyR1 channel and activation core domain. A total of 15 RYR1 mutant mouse strains were identified of which ten were heterozygous, three were compound heterozygous, and a further two were knockout. Porcine, avian, zebrafish, C. elegans, canine, equine, and drosophila model systems were also reported. Conclusions Over the past 30 years, there were 262 publications on MH and RYR1-RM preclinical model systems featuring more than 200 unique RYR1 variations tested in a broad range of species. Findings from these studies have set the foundation for therapeutic development for MH and RYR1-RM.

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Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia

Cited by 3 publications

References 41 publications

Structural Insights Into Disease Mutations of the Ryanodine Receptor

Structural Insights Into Disease Mutations of the Ryanodine Receptor

High‐resolution imaging and nano‐manipulation of biological structures on surface

Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990–2019

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