Author/Year | Genotype(s) | Title | Conclusions |
---|---|---|---|
Popovski ZT, et al. [239] 2016 | R615C | Associations of Biochemical Changes and Maternal Traits with Mutation 1843 (C > T) in the RYR1 Gene as a Common Cause for Porcine Stress Syndrome | Stress susceptible animals have an increased number of stillborn piglets and a reduced number of newborn piglets compared with heterozygous and normal animals |
Scheffler TL, et al. [240] 2014 | R615C | Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle | RyR1 R615C increased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1 R615C muscle influences mitochondrial proliferation and protein turnover |
Bina S, et al. [241] 2010 | R615C | Lymphocyte-based determination of susceptibility to malignant hyperthermia: a pilot study in swine | 4CmC stimulation of porcine lymphocytes induces increased adenosine formation in MHS cells relative to those from normal swine |
Liang X, et al. [242] 2009 | R615C | Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia | Purified RyR1(R615C) from MH susceptible porcine skeletal muscle shows significantly reduced oligomerization when compared to RyR1(WT), indicating a potential loss of intrinsic intermolecular control |
Ta TA, et al. [243] 2007 | R615C | Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C exhibits heightened sensitivity to dysregulation by non-coplanar 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) | A genetic mutation known to confer susceptibility to pharmacological agents also enhances sensitivity to an environmental contaminant |
Stinckens A, et al. [244] 2007 | R615C | The RYR1 g.1843C > T mutation is associated with the effect of the IGF2 intron3-g.3072G > A mutation on muscle hypertrophy | The effect of IGF2 on muscle growth might partially be mediated by the calpain/calpastatin system and that this is dependent on RYR1-mediated Ca2+ transport |
Murayama T, et al. [245] 2007 | R615C | Postulated role of interdomain interaction between regions 1 and 2 within type 1 ryanodine receptor in the pathogenesis of porcine malignant hyperthermia | Stimulation of the RyR1MHS channel caused by affected inter-domain interaction between regions 1 and 2 is an underlying mechanism for dysfunction of Ca2+ homoeostasis seen in the MH phenotype |
McKinney LC, et al. [262] 2006 | R615C | Characterization of Ryanodine Receptor–mediated Calcium Release in Human B Cells | Lymphocytes from MH pigs displayed an increased sensitivity to 4-CmC (EC50 decreased from 0.81 mM to 0.47 mM). The twofold magnitude of the shift was similar to that observed for 4-CmC–sensitive H-ryanodine binding in MH porcine skeletal muscle |
Gallant EM, et al. [246] 2004 | R615C | Caffeine sensitivity of native RyR channels from normal and malignant hyperthermic pigs: effects of a DHPR II–III loop peptide | In MH-susceptible pig muscles the caffeine sensitivity of native RyRs was enhanced, the sensitivity of RyRs to a skeletal II–III loop peptide was depressed, and an interaction between the caffeine and peptide CS activation mechanisms seen in normal RyRs was lost |
Zhao F, et al. [247] 2001 | R615C | Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity | Both the RyR1 and the RyR3, but not the RyR2, may be targets for dantrolene inhibition in vivo |
Gallant EM, et al. [248] 2001 | R615C | Arg(615) Cys substitution in pig skeletal ryanodine receptors increases activation of single channels by a segment of the skeletal DHPR II-III loop | Enhanced DHPR activation of RyRs may contribute to increased Ca2+ release from SR in MH-susceptible muscle |
Balog EM, et al. [249] 2001 | R615C | Divergent effects of the malignant hyperthermia-susceptible Arg(615)-- > Cys mutation on the Ca2+ and Mg2+ dependence of the RyR1 | Reduced Mg2+ inhibition of the MHS RyR1 compared with the normal RyR1 is due to both an enhanced selectivity of the MHS RyR1 A-site for Ca2+ over Mg2+ and a reduced Mg2+ affinity of the I-site |
Dietze B, et al. [250] 2000 | R615C | Malignant hyperthermia mutation Arg615Cys in the porcine ryanodine receptor alters voltage dependence of Ca2+ release | Arg615Cys does not only promote ligand-induced Ca2+ release but also the depolarization-induced release controlled by the DHP receptor voltage sensor |
Laver DR, et al. [251] 1997 | R615C | Reduced inhibitory effect of Mg2+ on ryanodine receptor-Ca2+ release channels in malignant hyperthermia | The cytoplasmic Mg2+ in vivo (approximately 1 mM), this Ca2+ Mg2+ inhibitory site will be close to fully saturated with Mg2+ in normal RyRs, but less fully saturated in MHS RyRs. Therefore, MHS RyRs should be more sensitive to any activating stimulus, which would readily account for the development of an MH episode |
Fruen BR, et al. [252] 1997 | R615C | Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors | Results demonstrate selective effects of dantrolene on skeletal muscle ryanodine receptors that are consistent with the actions of dantrolene in vivo and suggest a mechanism of action in which dantrolene may act directly at the skeletal muscle ryanodine receptor complex to limit its activation by calmodulin and C2+ |
Bašić I, et al. [253] 1997 | R615C | Stress syndrome: Ryanodine receptor (RYR1) gene in malignant hyperthermia in humans and pigs | This study confirmed application of a method for large-scale, rapid, accurate, DNA-based laboratory diagnosis of the mutation associated with susceptibility to porcine stress syndrome |
O’Driscoll S, et al. [254] 1996 | R615C | Calmodulin sensitivity of the sarcoplasmic reticulum ryanodine receptor from normal and malignant-hyperthermia-susceptible muscle | The central region of RYR1 is a potential binding domain for CaM in the absence of Ca2+. It is suggested that in vivo an enhanced CaM sensitivity of RYR1 might contribute to the abnormal high release of Ca2+ from the SR of MHS muscle |
Herrmann-Frank A, et al. [255] 1994 | R615C | 4-Chloro-m-cresol: a specific tool to distinguish between malignant hyperthermia-susceptible and normal muscle | 4-CmC is suggested to be a potent tool to distinguish between Ca2+ release from MHS and normal muscle |
Vogeli P, et al. [256] 1994 | R615C | Co-segregation of the malignant hyperthermia and the Arg615-Cys615 mutation in the skeletal muscle calcium release channel protein in five European Landrace and Pietrain pig breeds | DNA-based detection of the MH status in 238 MH-susceptible heterozygous (N/n) and homozygous (n/n) pigs was shown to be accurate, eliminating the 2% diagnostic error that is associated with the halothane challenge test |
Ledbetter MW, et al. [257] 1994 | R615C | Tissue distribution of ryanodine receptor isoforms and alleles determined by reverse transcription polymerase chain reaction | The normal (Arg615) and mutant (Cys615) ryr1 alleles were expressed in the brains of normal and malignant hyperthermia susceptible pigs, respectively. These results thus demonstrate expression of two ryr isoforms in each type of striated muscle, and all ryr isoforms in a number of regions of the nervous system. The wide distribution of ryr1 in the brain provides a possible neurogenic etiology of malignant hyperthermia |
Fagerlund T, et al. [258] 1994 | R615C | Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia | Other mutations must underlie the disorder in most Danish malignant hyperthermia-susceptible families, and the “pig mutation” is not a frequent cause of malignant hyperthermia susceptibility in Denmark |
Otsu K, et al. [259] 1992 | R615C | Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia | PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes |
Hogan K, et al. [260] 1992 | R615C | A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia | The cysteine-for-arginine mutation represents a shared calcium release channel pathogenesis between porcine malignant hyperthermia and a subset of mutations responsible for the human malignant hyperthermia syndrome |
Otsu K, et al. [261] 1991 | R615C | Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families | Substitution of T for C at nucleotide 1843 is the causative mutation in porcine MH |
Fujii J, et al. [27] 1991 | R615C | Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia | A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine |