scholarly journals Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia

2017 ◽  
Vol 4 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Remai Parker ◽  
Anja H. Schiemann ◽  
Elaine Langton ◽  
Terasa Bulger ◽  
Neil Pollock ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Functional Characterization ◽  
Central Core ◽  
Central Core Disease ◽  
Ryanodine Receptor 1

scholarly journals Functional Characterization of a Distinct Ryanodine Receptor Mutation in Human Malignant Hyperthermia-susceptible Muscle

1997 ◽  
Vol 272 (8) ◽  
pp. 5256-5260 ◽  
Author(s):  
Michael Richter ◽  
Lothar Schleithoff ◽  
Thomas Deufel ◽  
Frank Lehmann-Horn ◽  
Annegret Herrmann-Frank
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Functional Characterization ◽  
Malignant Hyperthermia Susceptible

scholarly journals Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein

2015 ◽  
Vol 2 (4) ◽  
pp. 421-432 ◽  
Author(s):  
Marine Cacheux ◽  
Ariane Blum ◽  
Muriel Sébastien ◽  
Anne Sophie Wozny ◽  
Julie Brocard ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Central Core ◽  
Central Core Disease

scholarly journals Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes

2006 ◽  
Vol 395 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Sylvie Ducreux ◽  
Francesco Zorzato ◽  
Ana Ferreiro ◽  
Heinz Jungbluth ◽  
Francesco Muntoni ◽  
...  
Keyword(s):  
Amino Acid ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Receptor Activation ◽  
Central Core ◽  
Central Core Disease ◽  
Amino Acid Substitutions ◽  
Time Data ◽  
Minicore Disease

More than 80 mutations in the skeletal muscle ryanodine receptor gene have been found to be associated with autosomal dominant forms of malignant hyperthermia and central core disease, and with recessive forms of multi-minicore disease. Studies on the functional effects of pathogenic dominant mutations have shown that they mostly affect intracellular Ca2+ homoeostasis, either by rendering the channel hypersensitive to activation (malignant hyperthermia) or by altering the amount of Ca2+ released subsequent to physiological or pharmacological activation (central core disease). In the present paper, we show, for the first time, data on the functional effect of two recently identified recessive ryanodine receptor 1 amino acid substitutions, P3527S and V4849I, as well as that of R999H, another substitution that was identified in two siblings that were affected by multi-minicore disease. We studied the intracellular Ca2+ homoeostasis of EBV (Epstein–Barr virus)-transformed lymphoblastoid cells from the affected patients, their healthy relatives and control individuals. Our results show that the P3527S substitution in the homozygous state affected the amount of Ca2+ released after pharmacological activation with 4-chloro-m-cresol and caffeine, but did not affect the size of the thapsigargin-sensitive Ca2+ stores. The other substitutions had no effect on either the size of the intracellular Ca2+ stores, or on the amount of Ca2+ released after ryanodine receptor activation; however, both the P3527S and V4849I substitutions had a small but significant effect on the resting Ca2+ concentration.

scholarly journals Divergent Activity Profiles of Type 1 Ryanodine Receptor Channels Carrying Malignant Hyperthermia and Central Core Disease Mutations in the Amino-Terminal Region

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130606 ◽  
Author(s):  
Takashi Murayama ◽  
Nagomi Kurebayashi ◽  
Toshiko Yamazawa ◽  
Hideto Oyamada ◽  
Junji Suzuki ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Terminal Region ◽  
Central Core ◽  
Central Core Disease ◽  
Amino Terminal ◽  
Disease Mutations

Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia

1993 ◽  
Vol 5 (1) ◽  
pp. 51-55 ◽  
Author(s):  
K. A. Quane ◽  
J.M.S. Healy ◽  
K. E. Keating ◽  
B. M. Manning ◽  
F. J. Couch ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Central Core ◽  
Central Core Disease

scholarly journals Reduced threshold for store overload-induced Ca2+ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease

2017 ◽  
Vol 474 (16) ◽  
pp. 2749-2761 ◽  
Author(s):  
Wenqian Chen ◽  
Andrea Koop ◽  
Yingjie Liu ◽  
Wenting Guo ◽  
Jinhong Wei ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Term Treatment ◽  
Central Core ◽  
Central Core Disease ◽  
Hek293 Cells ◽  
Polymorphic Ventricular Tachycardia ◽  
Long Term Treatment ◽  
The Impact ◽  
Common Defect

Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), whereas mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding ryanodine receptor (RyR) isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca2+ release during store Ca2+ overload, a process known as store overload-induced Ca2+ release (SOICR). Considering the similar locations of disease-associated RyR1 and RyR2 mutations in the RyR structure, we hypothesize that like CPVT-associated RyR2 mutations, MH/CCD-associated RyR1 mutations also enhance SOICR. To test this hypothesis, we determined the impact on SOICR of 12 MH/CCD-associated RyR1 mutations E2347-del, R2163H, G2434R, R2435L, R2435H, and R2454H located in the central region, and Y4796C, T4826I, L4838V, A4940T, G4943V, and P4973L located in the C-terminal region of the channel. We found that all these RyR1 mutations reduced the threshold for SOICR. Dantrolene, an acute treatment for MH, suppressed SOICR in HEK293 cells expressing the RyR1 mutants R164C, Y523S, R2136H, R2435H, and Y4796C. Interestingly, carvedilol, a commonly used β-blocker that suppresses RyR2-mediated SOICR, also inhibits SOICR in these RyR1 mutant HEK293 cells. Therefore, these results indicate that a reduced SOICR threshold is a common defect of MH/CCD-associated RyR1 mutations, and that carvedilol, like dantrolene, can suppress RyR1-mediated SOICR. Clinical studies of the effectiveness of carvedilol as a long-term treatment for MH/CCD or other RyR1-associated disorders may be warranted.

Next generation sequencing reveals ryanodine receptor 1 mutations in a Chinese central core disease cohort

2016 ◽  
Vol 54 (3) ◽  
pp. 432-438 ◽  
Author(s):  
Yan Zhao ◽  
Jing Hu ◽  
Zhe Zhao ◽  
Hongrui Shen ◽  
Qi Bing ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Ryanodine Receptor ◽  
Central Core ◽  
Central Core Disease ◽  
Next Generation ◽  
Ryanodine Receptor 1 ◽  
Generation Sequencing
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