Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Nelson, Thomas E.

doi:10.1172/jci111057

Cited by 137 publications

(50 citation statements)

References 31 publications

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“…Enhancement of CICR in patients with MH or in MH-susceptible pigs has also been demonstrated in FSR (22,67,123,174,193,201), [ 3 H]ryanodine binding to SR vesicles (91,174,267), and the single-channel activity of RyR1 (68,174,194,236,237,238). Although some studies failed to find increased Ca 2ϩ sensitivity of CICR (68,236,238), the maximum rate of Ca 2ϩ release was increased and, therefore, the absence of the increased Ca 2ϩ sensitivity does not rule out the possibility of the essential involvement of CICR in MH, as discussed below.…”

Section: B Malignant Hyperthermiamentioning

confidence: 91%

Calcium-Induced Calcium Release in Skeletal Muscle

Endo¹

2009

Physiological Reviews

257

223

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Calcium-induced calcium release (CICR) was first discovered in skeletal muscle. CICR is defined as Ca2+ release by the action of Ca2+ alone without the simultaneous action of other activating processes. CICR is biphasically dependent on Ca2+ concentration; is inhibited by Mg2+, procaine, and tetracaine; and is potentiated by ATP, other adenine compounds, and caffeine. With depolarization of the sarcoplasmic reticulum (SR), a potential change of the SR membrane in which the luminal side becomes more negative, CICR is activated for several seconds and is then inactivated. All three types of ryanodine receptors (RyRs) show CICR activity. At least one RyR, RyR1, also shows non-CICR Ca2+ release, such as that triggered by the t-tubule voltage sensor, by clofibric acid, and by SR depolarization. Maximum rates of CICR, at the optimal Ca2+ concentration in the presence of physiological levels of ATP and Mg2+ determined in skinned fibers and fragmented SR, are much lower than the rate of physiological Ca2+ release. The primary event of physiological Ca2+ release, the Ca2+ spark, is the simultaneous opening of multiple channels, the coordinating mechanism of which does not appear to be CICR because of the low probability of CICR opening under physiological conditions. The coordination may require Ca2+, but in that case, some other stimulus or stimuli must be provided simultaneously, which is not CICR by definition. Thus CICR does not appear to contribute significantly to physiological Ca2+ release. On the other hand, CICR appears to play a key role in caffeine contracture and malignant hyperthermia. The potentiation of voltage-activated Ca2+ release by caffeine, however, does not seem to occur through secondary CICR, although the site where caffeine potentiates voltage-activated Ca2+ release might be the same site where caffeine potentiates CICR.

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Section: B Malignant Hyperthermiamentioning

confidence: 91%

Calcium-Induced Calcium Release in Skeletal Muscle

Endo¹

2009

Physiological Reviews

257

223

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“…A notable exception is found among the earliest work investigating the effect of the MH R615C mutation on Ca 2ϩ handling by isolated SR membranes (13,24,25). Nelson and colleagues (13,24,25) …”

Section: Malignant Hyperthermia (Mh)mentioning

confidence: 99%

“…However, in comparison with the extensive investigations of the sensitivity of MHS RyR1 channels to cytosolic Ca 2ϩ and Mg 2ϩ , the effects of the MH R615C mutation on the luminal Ca 2ϩ sensitivity of the channel remain largely unexplored. A notable exception is found among the earliest work investigating the effect of the MH R615C mutation on Ca 2ϩ handling by isolated SR membranes (13,24,25). Nelson and colleagues (13,24,25) originally reported that the luminal Ca 2ϩ load required to trigger spontaneous SR Ca 2ϩ * This work was supported, in whole or in part, by National Institutes of Health Grants 1RO1HL75210 and RO1HL076433.…”

mentioning

confidence: 99%

Reduced Threshold for Luminal Ca2+ Activation of RyR1 Underlies a Causal Mechanism of Porcine Malignant Hyperthermia

Jiang

Chen

Xiao

et al. 2008

Journal of Biological Chemistry

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Malignant hyperthermia (MH)3 is an autosomal dominant, pharmacogenetic disorder of skeletal muscle. MH is triggered by volatile anesthetics (e.g. halothane) and depolarizing muscle relaxants and is characterized by muscle rigidity and a hypermetabolic state (1-5). MH also occurs in pigs, in which it is caused by stress and known as porcine stress syndrome (6, 7). A single point mutation, R615C, in the pig skeletal muscle ryanodine receptor RyR1 is responsible for all cases of porcine MH (6, 7). On the other hand, human MH has been linked to a large number of mutations in RyR1 (4,5,8). Some human RyR1 mutations have also been linked to central core disease, which is often associated with MH. Although the genetic basis of MH has been well defined, the molecular mechanisms by which RyR1 mutations confer MH susceptibility and volatile anesthetics and stress trigger MH are not completely understood.The pig model has proven invaluable in investigating the molecular basis of MH, and these studies have consistently demonstrated that Ca 2ϩ release from MH-susceptible (MHS) pig skeletal muscle or sarcoplasmic reticulum (SR) membrane vesicles is enhanced upon exposure to various stimuli (1, 4, 9 -14). However, to date no clear mechanistic basis of this enhanced responsiveness of MHS RyR1 channels to stimuli has emerged. For example, some studies reported that this enhanced activity of MHS RyR1 channels was associated with changes in the apparent sensitivity of the channel to cytosolic Ca 2ϩ or Mg 2ϩ , whereas others found no marked difference in the apparent sensitivity to cytosolic Ca 2ϩ activation between MHS and normal RyR1 channels (1,(13)(14)(15)(16)(17)(18)(19)(20). Hence, the intrinsic properties of the RyR1 channel that are altered by the MH R615C mutation have remained undefined.Increasing evidence has highlighted the importance not only of cytosolic Ca 2ϩ , but also of luminal Ca 2ϩ , in controlling the activity of the RyR channel (21-23). However, in comparison with the extensive investigations of the sensitivity of MHS RyR1 channels to cytosolic Ca 2ϩ and Mg 2ϩ , the effects of the MH R615C mutation on the luminal Ca 2ϩ sensitivity of the channel remain largely unexplored. A notable exception is found among the earliest work investigating the effect of the MH R615C mutation on Ca 2ϩ handling by isolated SR membranes (13,24,25). Nelson and colleagues (13,24,25)

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“…Skeletal muscle sarcoplasmic reticulum from porcine diaphragm was prepared following the method given by I.e. (12). Crude membrane ffactions of different muscle types were isolated s described in 1. c. (8).…”

Section: Methodsmentioning

confidence: 99%

An Enzyme Immunoassay for Phospholamban

Holtzhauer¹

1987

Clinical Chemistry and Laboratory Medicine

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Summary: Phospholamban, a phosphorylatable protein of the cardiac sarcoplasmic reticulum, has been esümated by a semi-quantitative immunoassay. It can be determinated in purified membrane preparations äs well äs in crude fractions of cardiac muscle membranes, regardless of the phosphorylation state of the phosphoprotein. The content of phospholamban in mammalian heart muscle membrane vesicles correlates with the activity of the calcium/magnesium-dependent ATPase with the exception of the oxalate-loaded membrane preparations. This observation indicates that phospholamban and the calcium transporting enzyme are localized at different sites in cardiac sarcoplasmic reticulum.

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Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Cited by 137 publications

References 31 publications

Calcium-Induced Calcium Release in Skeletal Muscle

Calcium-Induced Calcium Release in Skeletal Muscle

Reduced Threshold for Luminal Ca2+ Activation of RyR1 Underlies a Causal Mechanism of Porcine Malignant Hyperthermia

An Enzyme Immunoassay for Phospholamban

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