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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, constituting the 1990 International Lecture of the Biophysical Society, research is described in two areas in which molecular genetic techniques were used to dissect problems related to sarcoplasmic reticulum proteins: the use of site-directed mutagenesis to gain insight into the mechanism of Ca2+ transport by the Ca2(+)-ATPase; and the use of cloning and genetic linkage analysis to identify the Ca2+ release channel (RYR1) gene as a candidate gene for the predisposition to malignant hyperthermia, a neuromuscular disease of humans and domestic animals.
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PMID:Molecular tools to elucidate problems in excitation-contraction coupling. 217 55

Excised muscles from patients with myotonia or periodic paralysis were subjected to the in vitro contracture test for susceptibility to malignant hyperthermia (MH). In a group of 44 patients, this standard test gave four positive, 10 equivocal and 30 negative results. The results for 27 control muscles from normal subjects were negative. When the test was performed with less than normal concentrations of contracture-triggering substances (caffeine less than or equal to 2 mmol litre-1, less than or equal to 2% halothane), 70% of the muscles from the patients and only 15% of the controls responded with small contractures (less than 0.2 g). These results should not be taken to indicate that the patients have the genetic trait for MH. The positive and equivocal test results, in addition to the slight contractures, may be accounted for by the electrical after-activity in the cases of pure myotonia, and by increased resting myoplasmic [Ca2+] in myotonic dystrophy. This shows that the in vitro contracture test lacks specificity.
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PMID:Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? 224 48

Anaesthetic-induced increases in cytoplasmic free Ca2+ have been reported to be greater in lymphocytes from malignant hyperthermia (MH) susceptible patients than in those from controls, suggesting that this may be the basis for a less invasive test for MH susceptibility. In the present study the cytoplasmic Ca2+ concentrations of lymphocytes were monitored with indo-1 in 14 control subjects (nine fasted and five nonfasted) and five fasted MH susceptible and three fasted nonsusceptible patients, diagnosed by the halothane and caffeine contracture tests. No relationship was observed between MH susceptibility and Ca2+ concentrations in lymphocytes in the absence or presence of halothane. There was, however, a relationship in control subjects between fasting and the response of lymphocytes to halothane, with the halothane-induced Ca2+ increase being considerably larger in nonfasted subjects.
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PMID:Importance of fasting in the lymphocyte calcium test for malignant hyperthermia. 227 24

Calcium release from sarcoplasmic reticulum was investigated using skinned fibers isolated from rabbit semitendinosus and psoas muscles, representative of slow and fast fibers, respectively. In both types of fibers, halothane at the concentration of 0.03% (v/v) enhanced the Ca2(+)-induced calcium release. In the absence of cytoplasmic free Ca2+, halothane induced calcium release in a dose-dependent manner, with a similar sensitivity for both semitendinosus and psoas fibers. These results are discussed in connection with muscular diseases such as malignant hyperthermia in which the crisis is triggered during anesthesia by halothane.
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PMID:Effects of halothane on calcium release from sarcoplasmic reticulum of rabbit psoas and semitendinosus skinned muscle fibers. 229 53

This study provides the first comprehensive characterisation of the calcium (Ca) homeostasis defects found in muscle and lymphocytes of a malignant hyperthermia (MH)-susceptible dog. Novel findings regarding this dog are reported, compared to controls. First, a canine stress syndrome occurs, analogous to the porcine stress syndrome; susceptibility can be identified by exercise challenge testing. Secondly, caffeine causes Ca release from muscle sarcoplasmic reticulum in a greater amount and at a greater rate. Thirdly, there is a compensatory increase in Ca sequestration by sarcoplasmic reticulum. Fourthly, lymphocytes have lower cytosolic-free Ca and a greater ability to prevent Ca increase. Halothane increases Ca by a greater amount and rate. Fifthly, muscle is more resistant to the contracture-producing effects of caffeine, as occurs in the non-rigid variant of MH susceptibility in man. This resistance, despite increased caffeine-induced release through the Ca channel, may be attributable to increased Ca sequestration by sarcoplasmic reticulum. Finally, erythrocyte osmotic fragility and creatine kinase tests fail to distinguish between the MH-susceptible dog and controls.
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PMID:Canine stress syndrome/malignant hyperthermia susceptibility: calcium-homeostasis defect in muscle and lymphocytes. 230 Jul 6

Calcium accumulation by the sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia-susceptible (MH+) and non-susceptible (MH-) humans and pigs was investigated using a calcium electrode at 35 degrees C. Sarcoplasmic reticulum of MH+ humans and pigs showed normal Ca2+ accumulation, with no difference being observed in the rate and the time taken to achieve maximal accumulation. However, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum in MH+ humans and pigs is considerably less stable than normal after prolonged ageing of the whole muscle homogenate preparations in ice. In MH+ patients, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum showed a decline of 62% at 22 h ageing and 70% at 48 h ageing, as compared with a reduction of only 23% in MH- patients. In MH+ pigs, the sarcoplasmic reticulum showed a 96% deterioration in the capacity for Ca2+ accumulation as compared with a loss of only 40% in MH- pigs at 7 h ageing in ice. In both humans and pigs, the decline in Ca2+ accumulation was prevented by incubating the whole muscle homogenate preparations for 2 h at 35 degrees C prior to ageing the preparations. The diminished Ca2+ accumulating capacity of the sarcoplasmic reticulum in whole muscle homogenate preparations of MH-susceptible individuals in our experimental protocol provides a potential diagnostic test for malignant hyperthermia susceptibility.
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PMID:Calcium accumulation by sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia diagnostic patients and pigs. 230 11

Previous studies have demonstrated a defect associated with the calcium release mechanism of sarcoplasmic reticulum (SR) from individuals susceptible to malignant hyperthermia (MH). To examine whether SR calcium release channels were indeed altered in MH, SR vesicles were purified from normal and MH susceptible (MHS) porcine muscle. The Ca2+ dependence of calcium efflux rates from 45Ca2(+)-filled SR vesicles was then compared with the Ca2+ dependence of single-channel recordings of SR vesicles incorporated into planar lipid bilayers. The rate constants of 45Ca2+ efflux from MHS SR were two to threefold larger than from normal SR over a wide range of myoplasmic Ca2+. Normal and MHS single channels were progressively activated in a similar fashion by cis Ca2+ from pCa 7 to 4. However, below pCa 4, normal channels were inactivated by cis Ca2+, whereas MHS channels remained open for significantly longer times. The altered Ca2+ dependence of channel inactivation in MHS SR was also evident when Ca2+ was increased on the trans side while cis Ca2+ was held constant. We propose that a defect in a low-affinity Ca2+ binding site is responsible for the altered gating of MHS SR channels. Such a defect could logically result from a mutation in the gene encoding the calcium release channel, providing a testable hypothesis for the molecular basis of this inherited disorder.
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PMID:Abnormal ryanodine receptor channels in malignant hyperthermia. 230 96

When compared to normal pig sarcoplasmic reticulum (SR), SR from malignant hyperthermia susceptible (MHS) porcine skeletal muscle has been shown to exhibit an increased rate of calcium release, as well as alterations in [3H]ryanodine-binding activity in the presence of microM Ca2+ (Mickelson et al., 1988, J. Biol. Chem. 263, 9310). In the present study, various stimulators (adenine nucleotides and caffeine) and inhibitors (ruthenium red and Mg2+) of the SR calcium release channel were examined for effects on MHS and normal SR [3H]ryanodine binding. The apparent affinity of the MHS SR receptor for ryanodine in the presence of 10 mM ATP (Kd = 6.0 nM) or 10 mM caffeine (Kd = 28 nM) was significantly greater than that of the normal SR (Kd = 8.5 and 65 nM in 10 mM ATP or caffeine, respectively), the Bmax (12-16 pmol/mg) was similar in all cases. The Ca2+(0.5) for inhibition of [3H]ryanodine binding in the presence of 5 mM AMPPNP (238 vs 74 microM for MHS and normal SR, respectively) and the Ca2+(0.5) for stimulation of [3H]ryanodine binding in the presence of 5 mM caffeine (0.049 vs 0.070 microM for MHS and normal SR, respectively) were also significantly different. Furthermore, in the presence of optimal Ca2+, MHS SR [3H]ryanodine binding was more sensitive to caffeine stimulation (C0.5 of 1.7 vs 3.4 mM) and was less sensitive to ruthenium red (C0.5 of 1.9 vs 1.2 microM) or Mg2+ inhibition (C0.5 of 0.34 vs 0.21 mM) than was normal SR. These results further support the hypothesis that differences in the ryanodine/receptor calcium release channel regulatory properties are responsible for the abnormal calcium releasing activity of MHS SR.
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PMID:Stimulation and inhibition of [3H]ryanodine binding to sarcoplasmic reticulum from malignant hyperthermia susceptible pigs. 232 64

Halothane in concentrations exceeding 1.2 mmol litre-1 increased (P less than 0.05) the apparent intracellular concentration of calcium in lymphocytes from 12 patients being tested for susceptibility to malignant hyperthermia (MH) using the fluorescent Ca2+ indicator, fura2. There was no difference in [Ca2+]i between lymphocytes from patients found to be MH susceptible (n = 5) on in vitro contracture testing with halothane and caffeine and those from MH negative patients (n = 6). Thus determination of [Ca2+]i in lymphocytes after exposure to halothane could not be used as a diagnostic test for MH susceptibility.
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PMID:Cytosolic free calcium concentrations in lymphocytes from malignant hyperthermia susceptible patients. 232 83

It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium [( Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]i and [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]i and [Mg2+]i were determined by means of ion-selective microelectrodes. The resting [Ca2+]i in normal muscle fibers was 0.11 +/- 0.01 microM (mean +/- SEM), whereas in the MH muscles the resting [Ca2+]i was 0.36 +/- 0.01 microM. In neither group was the resting [Ca2+]i modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]i associated with the syndrome from 7.29 +/- 0.43 microM in untreated animals to 0.84 +/- 0.03 microM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+]i were not different in control and MH-susceptible muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine. 236 Jul 20


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