Propofol-Induced Changes in Myoplasmic Calcium Concentrations in Cultured Human Skeletal Muscles from RYR1 Mutation Carriers

Migita, Takako; Mukaida, Keiko; Kawamoto, Masashi; Kobayashi, Masako; Nishino, Ichizo; Yuget, O

doi:10.1177/0310057x0703500606

Cited by 9 publications

(8 citation statements)

References 13 publications

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“…In Dainese et al [ 15 ], we also showed that incidence of mortality in CASQ1-null mice during exposure to both halothane and heat is significantly greater in males than in females, a finding in line with some epidemiological studies conducted in humans, which reported a male prevalence of ~3 : 1 to 4 : 1 [ 25 – 27 ]. To date, the reason for this gender difference in humans and in CASQ1-null mice remains unclear.…”

Section: Introductionsupporting

confidence: 87%

Estrogens Protect Calsequestrin‐1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Michelucci

Boncompagni

Canato

et al. 2017

Oxidative Medicine and Cellular Longevity

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Oxidative stress has been proposed to play a key role in malignant hyperthermia (MH), a syndrome caused by excessive Ca2+ release in skeletal muscle. Incidence of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure to halothane and heat (a syndrome closely resembling human MH) is far greater than that in females. To investigate the possible role of sex hormones in this still unexplained gender difference, we treated male and female CASQ1-null mice for 1 month, respectively, with Premarin (conjugated estrogens) and leuprolide (GnRH analog) and discovered that during exposure to halothane and heat Premarin reduced the mortality rate in males (79–27% and 86–20%), while leuprolide increased the incidence of mortality in females (18–73% and 24–82%). We then evaluated the (a) responsiveness of isolated muscles to temperature and caffeine, (b) sarcoplasmic reticulum (SR) Ca2+ release in single fibers, and (c) oxidative stress and the expression levels of main enzymes involved in the regulation of the redox balance in muscle. Premarin treatment reduced the temperature and caffeine sensitivity of EDL muscles, normalized SR Ca2+ release, and reduced oxidative stress in males, suggesting that female sex hormones may protect mice from lethal hyperthermic episodes by reducing both the SR Ca2+ leak and oxidative stress.

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Section: Introductionsupporting

confidence: 87%

Estrogens Protect Calsequestrin‐1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Michelucci

Boncompagni

Canato

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Thirty-four patients were enrolled in this study (Table 1), including 17 individuals described in a previous study 17,18 . Four patients (numbers 5, 6, 15 and 16) experienced MH events diagnosed as rank 5 or 6 according to clinical grading scale 19 during general anaesthesia.…”

Section: Patientsmentioning

confidence: 99%

“…The CICR rate was measured according to Endo's method [15][16][17][18] . In brief, bundles of skeletal muscle fibres 5 to 6 mm in width and 10 to 15 mm in length were dissected into smaller pieces, and these pieces were isolated in the relaxing solution under a stereomicroscope.…”

Section: Calcium-induced Calcium Release Rate Testmentioning

confidence: 99%

Analysis of Human Cultured Myotubes Responses Mediated by Ryanodine Receptor 1

Kobayashi

Mukaida

Migita

et al. 2011

Anaesth Intensive Care

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Malignant hyperthermia is a life-threatening condition caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Identifying patients predisposed to malignant hyperthermia is done through the Ca-induced Ca release test in Japan. We examined the intracellular calcium concentration in human cultured muscle cells and compared the sensitivity of myotubes to ryanodine receptor type 1 activators based on the Ca-induced Ca release rate. We assessed the utility of this method as an identifying test for predisposition to malignant hyperthermia. Muscle specimens were obtained from 34 individuals undergoing the Ca-induced Ca release test. We cultured myotubes from residual material and monitored changes in intracellular calcium concentration after exposure to the ryanodine receptor type 1 activators caffeine, halothane and 4-chloro-m-cresol by measuring fura-2 fluorescence. We determined the half maximal effective concentrations (EC 50) for the test compounds in each myotube and calculated cutoff points using receiver operating characteristic curves. Seventeen patients each were classified into the accelerated and non-accelerated groups based on their Ca-induced Ca release rate. The EC 50 values for caffeine, halothane and 4-chloro-m-cresol of the accelerated group were significant lower than those of the nonaccelerated group (P <0.001, P <0.001 and P <0.001, respectively). The calculated cutoff points of EC 50 values for caffeine, halothane and 4-CmC were 3.62 mM, 2.28 mM and 197 μM, respectively. An increased sensitivity to ryanodine receptor type 1 activators was seen in myotubes in the accelerated group. This functional test on human cultured myotubes indicates that the alteration of their intracellular Ca 2+ homeostasis may identify the predisposition to malignant hyperthermia.

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“…Case no. 2 had a C>T point mutation in RYR1 exon 47 at position 7522 and the pathologic diagnosis was myopathic changes with some fibres exhibiting cores or core-like structures, type 1 fibre predominance and type 2b fibredeficiency 10,17 . The non-accelerated group did not include individuals with muscle disease or anyone who reported a previous MH episode.…”

Section: Patientsmentioning

confidence: 99%

“…However, its safety has not been confirmed by studies at the human cellular level on Ca 2+ homeostasis. Recently, we examined the effects of propofol on Ca 2+ homeostasis in isolated human myotubes from two patients carrying RYR1 mutations linked to MH 17 . With the addition of more cases, the aim of this study was to investigate the safety of propofol and its mode of action upon skeletal muscle cells.…”

mentioning

confidence: 99%

Effects of Propofol on Calcium Homeostasis in Human Skeletal Muscle

Migita

Mukaida

Hamada

et al. 2009

Anaesth Intensive Care

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Malignant hyperthermia is a pharmacogenetic skeletal muscle disorder of intracellular calcium (Ca 2+) homeostasis with an autosomal dominant inheritance. The objective of this study was to investigate the safety of propofol by investigating its effects on calcium homeostasis and its effect sites in human skeletal muscles. Muscle specimens were obtained from 10 individuals with predisposition to malignant hyperthermia. In skinned fibre experiments, we measured the effects of propofol on the Ca 2+-induced Ca 2+ release and the uptake of Ca 2+ into the sarcoplasmic reticulum. Ca 2+ imaging in primary myotubes was employed to analyse propofol-mediated alternations in the Ca 2+ regulation and propofol-induced Ca 2+ responses in the presence of Ca 2+ channel blocker or Ca 2+-induced Ca 2+ release inhibitor. Increased Ca 2+ release from the sarcoplasmic reticulum and inhibition of Ca 2+ uptake into the sarcoplasmic reticulum were not observed with 100 μM propofol. A rise of Ca 2+ was not seen under 100 μM propofol and the EC 50 value for propofol was 274.7±33.9 μM, which is higher than the clinical levels for anaesthesia. Propofolinduced Ca 2+ responses were remarkably attenuated in the presence of Ca 2+ channel blocker or Ca 2+-induced Ca 2+ release inhibitor compared with the results obtained with caffeine. We conclude firstly that propofol is safe for individuals with predisposition to malignant hyperthermia when it is used within the recommended clinical dosage range, and secondly that its mode of action upon ryanodine receptors is likely to be different from that of caffeine.

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Propofol-Induced Changes in Myoplasmic Calcium Concentrations in Cultured Human Skeletal Muscles from RYR1 Mutation Carriers

Cited by 9 publications

References 13 publications

Estrogens Protect Calsequestrin‐1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Estrogens Protect Calsequestrin‐1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Analysis of Human Cultured Myotubes Responses Mediated by Ryanodine Receptor 1

Effects of Propofol on Calcium Homeostasis in Human Skeletal Muscle

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