Anesthetic‐and heat‐induced sudden death in calsequestrin‐1‐knockout mice

Dainese, Marco; Quarta, Marco; Lyfenko, Alla D.; Paolini, Cecilia; Canato, Marta; Reggiani, Carlo; Dirksen, Robert T.; Protasi, Feliciano

doi:10.1096/fj.08-121335

Cited by 103 publications

(197 citation statements)

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“…Three days after the constant load test, all mice were subjected to a heat challenge in an environmental chamber (41°C for 1 h). Consistent with previous publications [21,23], mortality rate during the heat stress protocol was significantly higher in CASQ1-null than in WT mice: 86% versus 18%, respectively (Figures 4(a) and 4(b)). Though, the mortality rate of CASQ1-null mice was reduced to only 16% after two months of aerobic training (Figures 4(a) and 4(b)).…”

Section: Aerobic Training Protects Male Casq1-null Mice Fromsupporting

confidence: 92%

“…Three days after the constant load test (see above), all mice were subjected to a heat stress protocol. Animals were placed in an environmental chamber in which temperature was maintained at 41°C, 1 h [21]. During exposure to heat, core body temperature was measured using a rectal thermometer taped to the tail of the animals and recorded every 5 min throughout the duration of heat challenge.…”

Section: Aerobic Trainingmentioning

confidence: 99%

“…Cytosolic Ca 2+ levels have been shown to be slightly elevated in CASQ1-null fibers [18,21,23] and may lead to an increased need of Ca 2+ removal from the cytosol [37,64]. For this reason, we measured SERCA activity in microsomal membranes of gastrocnemius muscles, estimated as production of P i in the presence of ATP (Figure 6(a)).…”

Section: Calpain Activity Was Reduced In Muscles Ofmentioning

confidence: 99%

“…The correlation between MH and EHS is also supported by evidence collected in animal models: (a) in porcine stress syndrome (PSS), swine carrying a point mutation in RYR1 trigger MH episodes in response to halothane administration but also following exposure to either heat or emotional/ physical stress [14,15]; (b) knock-in mice carrying gainof-function point mutations in RYR1 linked to MH in humans exhibit heat-and anesthetic-induced MH episodes [16,17]. In addition, we discovered that male mice lacking calsequestrin-1 (CASQ1-null), the main Ca 2+ -binding protein located in the lumen of SR terminal cisternae that modulates RyR1 opening probability [18][19][20], exhibit lethal hyperthermic episodes when exposed to anesthetics, heat, and strenuous exercise [18,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Aerobic Training Prevents Heat-Strokes in Calsequestrin 1 Knockout Mice by Reducing Oxidative Stress

Guarnier

Serano

Michelucci

et al. 2018

Biophysical Journal

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Calsequestrin-1 knockout (CASQ1-null) mice suffer lethal episodes when exposed to strenuous exercise and environmental heat, crises known as exertional/environmental heatstroke (EHS). We previously demonstrated that administration of exogenous antioxidants (N-acetylcysteine and trolox) reduces CASQ1-null mortality during exposure to heat. As aerobic training is known to boost endogenous antioxidant protection, we subjected CASQ1-null mice to treadmill running for 2 months at 60% of their maximal speed for 1 h, 5 times/week. When exposed to heat stress protocol (41°C/1 h), the mortality rate of CASQ1-null mice was significantly reduced compared to untrained animals (86% versus 16%). Protection from heatstrokes was accompanied by a reduced increase in core temperature during the stress protocol and by an increased threshold of response to caffeine of isolated extensor digitorum longus muscles during in vitro contracture test. At cellular and molecular levels, aerobic training (i) improved mitochondrial function while reducing their damage and (ii) lowered calpain activity and lipid peroxidation in membranes isolated from sarcoplasmic reticulum and mitochondria. Based on this evidence, we hypothesize that the protective effect of aerobic training is essentially mediated by a reduction in oxidative stress during exposure of CASQ1-null mice to adverse environmental conditions.

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Section: Aerobic Training Protects Male Casq1-null Mice Fromsupporting

confidence: 92%

Section: Aerobic Trainingmentioning

confidence: 99%

Section: Calpain Activity Was Reduced In Muscles Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aerobic Training Prevents Heat-Strokes in Calsequestrin 1 Knockout Mice by Reducing Oxidative Stress

Guarnier

Serano

Michelucci

et al. 2018

Biophysical Journal

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“…It should be pointed out that all the patients identified so far were heterozygous for the causative CASQ1 mutation, while the functional studies were performed on homozygous mutated calsequestrin 1 molecules. Thus it is likely that the mild phenotype of the patients may be due to the presence of wild type calsequestrin 1 molecules within the SR. Of interest, CASQ1 KO mice exhibit heat intolerance leading to an MH-like phenotype, enhanced oxidative stress, mitochondrial damage and reduced levels of releasable Ca 2+ [74,75].…”

Section: Casq1 Mutations and Vacuolar Aggregate Myopathymentioning

confidence: 99%

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

Treves

Jungbluth

Voermans

et al. 2017

Seminars in Cell & Developmental Biology

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a b s t r a c tThe physiological process by which Ca 2+ is released from the sarcoplasmic reticulum is called excitationcontraction coupling; it is initiated by an action potential which travels deep into the muscle fiber where it is sensed by the dihydropyridine receptor, a voltage sensing L-type Ca 2+ channel localized on the transverse tubules. Voltage-induced conformational changes in the dihydropyridine receptor activate the ryanodine receptor Ca 2+ release channel of the sarcoplasmic reticulum. The released Ca 2+ binds to troponin C, enabling contractile thick-thin filament interactions. The Ca 2+ is subsequently transported back into the sarcoplasmic reticulum by specialized Ca 2+ pumps (SERCA), preparing the muscle for a new cycle of contraction. Although other proteins are involved in excitation-contraction coupling, the mechanism described above emphasizes the unique role played by the two Ca 2+ channels (the dihydropyridine receptor and the ryanodine receptor), the SERCA Ca 2+ pumps and the exquisite spatial organization of the membrane compartments endowed with the proteins responsible for this mechanism to function rapidly and efficiently. Research over the past two decades has uncovered the fine details of excitation-contraction coupling under normal conditions while advances in genomics have helped to identify mutations in novel genes in patients with neuromuscular disorders. While it is now clear that many patients with congenital muscle diseases carry mutations in genes encoding proteins directly involved in Ca 2+ homeostasis, it has become apparent that mutations are also present in genes encoding for proteins not thought to be directly involved in Ca 2+ regulation. Ongoing research in the field now focuses on understanding the functional effect of individual mutations, as well as understanding the role of proteins not specifically located in the sarcoplasmic reticulum which nevertheless are involved in Ca 2+ regulation or excitation-contraction coupling. The principal challenge for the future is the identification of drug targets that can be pharmacologically manipulated by small molecules, with the ultimate aim to improve muscle function and quality of life of patients with congenital muscle disorders. The aim of this review is to give an overview of the most recent findings concerning Ca 2+ dysregulation and its impact on muscle function in patients with congenital muscle disorders due to mutations in proteins involved in excitation-contraction coupling and more broadly on Ca 2+ homeostasis.

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Intracellular Calcium

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Anesthetic‐and heat‐induced sudden death in calsequestrin‐1‐knockout mice

Cited by 103 publications

References 63 publications

Aerobic Training Prevents Heat-Strokes in Calsequestrin 1 Knockout Mice by Reducing Oxidative Stress

Aerobic Training Prevents Heat-Strokes in Calsequestrin 1 Knockout Mice by Reducing Oxidative Stress

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

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