Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle.

Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle.
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从恶性高热易感猪肌肉中分离出的肌浆网囊泡增强了 Ca2 诱导的钙释放。

DOI:
10.1016/0005-2736(86)90234-8
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发表时间:
1986
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Louis,CF
Louis,CF
中科院分区:
--
文献类型:
--
作者:
Mickelson,JR;Ross,JA;Reed,BK;Louis,CF

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为了进一步确定骨骼肌疾病恶性高热(MH)中肌浆网钙积累和释放的可能参与,我们检查了从正常和MH易感猪肌肉中分离的肌浆网部分的各种特性。在不连续的蔗糖密度梯度上进一步分离来自末端池的富含囊泡的肌浆网制剂(Meissner, G.(1984) J. Biol.)。化学,259,2365-2374)。所得的mh敏感肌浆网和正常肌浆网部分,指定为f0f4,在产量、胆固醇和磷脂含量或尼群地平结合能力方面没有差异。钙积累(22°C时为0.27 μmol Ca/mg / min)、ca2 +- atp酶活性(22°C时为0.98 μmol P i/mg / min)和钙螯合素含量在mh敏感肌和正常肌浆网部分f3中也相似。为了检测肌浆网钙的释放,f3部分囊泡被动加载45钙(约。40 nmol Ca/mg),并迅速稀释到指定ca2 +浓度的培养基中。经1 μM ca2 +稀释后,5 s后测得的ca2 +依赖性钙释放量在mh敏感肌浆网中显著高于正常肌浆网,分别为钙负荷的65.9±2.8%和47.7±3.9%。与正常肌浆网相比,h敏感肌浆网对ca2 +的钙释放(5 s值)的c12对ca2 +的刺激也似乎向更高的ca2 +敏感性转移。丹trolene对f3部位钙释放无影响,而氟烷(0.1 ~ 0.5 mM)对h敏感肌浆网和正常肌浆网钙释放的影响相似(5 s)。此外,与正常肌浆网相比,ca2 +抑制作用较弱,而ATP和咖啡因则更有效地刺激ca2 +依赖性钙从mh易感肌浆网释放。我们的研究结果表明,虽然肌浆网钙积累在MH中似乎不受影响,但肌浆网ca2 +诱导的钙释放机制的某些方面发生了改变。虽然ca2 +诱导的肌浆网原位钙释放机制的作用尚不清楚,但我们的研究结果表明,肌浆网钙释放调节的异常可能在MH综合征中起重要作用。
To further define the possible involvement of sarcoplasmic reticulum calcium accumulation and release in the skeletal muscle disorder malignant hyperthermia (MH), we have examined various properties of sarcoplasmic reticulum fractions isolated from normal and MH-susceptible pig muscle. A sarcoplasmic reticulum preparation enriched in vesicles derived from the terminal cisternae, was further fractionated on discontinuous sucrose density gradients (Meissner, G.(1984) J. Biol. Chem. 259, 2365–2374). The resultant MH-susceptible and normal sarcoplasmic reticulum fractions, designated F 0 F 4, did not differ in yield, cholesterol and phospholipid content, or nitrendipine binding capacity. Calcium accumulation (0.27 μmol Ca/mg per min at 22° C), Ca 2+-ATPase activity (0.98 μmol P i/mg per min at 22° C), and calsequestrin content were also similar for MH-susceptible and normal sarcoplasmic reticulum fraction F 3. To examine sarcoplasmic reticulum calcium release, fraction F 3 vesicles were passively loaded with 45 Ca (approx. 40 nmol Ca/mg), and rapidly diluted into a medium of defined Ca 2+ concentration. Upon dilution into 1 μM Ca 2+, the extent of Ca 2+-dependent calcium release measured after 5 s was significantly greater for MH-susceptible than for normal sarcoplasmic reticulum, 65.9±2.8% vs. 47.7±3.9% of the loaded calcium, respectively. The C 1 2 for Ca 2+ stimulation of this calcium release (5 s value) from MH-susceptible sarcoplasmic reticulum also appeared to be shifted towards a higher Ca 2+-sensitivity when compared to normal sarcoplasmic reticulum. Dantrolene had no effect on calcium release from fraction F 3, however, halothane (0.1–0.5 mM) increased the extent of calcium release (5 s) similarly in both MH-susceptible and normal sarcoplasmic reticulum. Furthermore, Mg 2+ was less effective at inhibiting, while ATP and caffeine were more effective in stimulating, this Ca 2+-dependent release of calcium from MH-susceptible, when compared to normal sarcoplasmic reticulum. Our results demonstrate that while sarcoplasmic reticulum calcium-accumulation appears unaffected in MH, aspect (s) of the sarcoplasmic reticulum Ca 2+-induced calcium release mechanism are altered. Although the role of the Ca 2+-induced calcium release mechanism of sarcoplasmic reticulum in situ is not yet clear, our results suggest that an abnormality in the regulation of sarcoplasmic reticulum calcium release may play an important role in the MH syndrome.
分离的肌浆网中的钙快速释放是通过附着的横向管状系统触发的。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Ikemoto,N;Antoniu,B;Kim,DH
通讯作者: Kim,DH
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发表时间: 1979
影响因子: 5
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发表时间: 1975
影响因子: 9.8
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DOI: 10.1002/jsfa.2740271209
发表时间: 1976
影响因子: 4.1
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通讯作者: A. Cheah
DOI: 10.1016/s0006-3495(85)83918-7
发表时间: 1985-01-01
影响因子: 3.4
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