High intracellular [Ca2+] alters sarcoplasmic reticulum function in skinned skeletal muscle fibres of the rat
High intracellular [Ca2+] alters sarcoplasmic reticulum function in skinned skeletal muscle fibres of the rat
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DOI：
10.1111/j.1469-7793.1999.0815n.x
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发表时间：
1999-09-01
影响因子：
5.5
通讯作者：
Cellini, MA
中科院分区：
文献类型：
--
作者：
Lamb, GD;Cellini, MA
1.暴露于高细胞内[Ca 2 +]对肌浆网（SR）功能的影响。方法：1.以大鼠趾长伸肌肌纤维为材料，用咖啡因测定肌浆网Ca ~（2+）含量. 15秒暴露于50 μ M的Ca 2+不可逆地降低了SR的能力，负载/保留Ca 2+和完全废除去极化诱导的Ca 2+释放，而90秒暴露于10 μ M的Ca 2+没有检测到的影响，无论是功能。净SR Ca 2+摄取的减少：（a）在50 μ M Ca 2+处理时接近最大值，（B）与电压传感器功能无关，和（c）持续不变> 20 min。这种减少主要是由于SR中Ca 2+渗漏增加了3倍。这种增加的渗漏基本上不被10 mM Mg 2+的存在所阻断或2 μ M钌红。暴露于高[Ca 2 +]对SR功能的不利影响也可以通过SR在面对浴溶液中升高的[Ca 2 +]时在皮肤纤维内维持低[Ca 2 +]的能力降低来观察。当浸泡在含有1.5 μ M Ca 2+（0.75 mM CaEGTA-EGTA）的溶液中时，去皮纤维在许多分钟内仅产生低的力响应，但在高[Ca 2 +]处理（暴露于50 μ M Ca 2 + 15 s）后，它们显示出大的、稳定的或振荡的力响应。这些研究结果表明，除了解偶联的Ca 2+释放通道的电压传感器，暴露的皮肤纤维高[Ca 2 +]导致持续增加静息Ca 2+流出SR。这种流出在一个完整的纤维将改变SR，细胞质和细胞外溶液之间的Ca 2+的分布。这些结果可能与低频疲劳的基础以及肌肉中可能的其他条件有关。
1. The effect on sarcoplasmic reticulum (SR) function of exposure to high intracellular [Ca2+]. was studied in mechanically skinned fibres from the extensor digitorum longus muscle of the rat, using caffeine to assay the SR Ca2+ content.2. A 15 s exposure to 50 mu M Ca2+ irreversibly reduced the ability of the SR to load/retain Ca2+ and completely abolished depolarization-induced Ca2+ release, whereas a 90 s exposure to 10 mu M Ca2+ had no detectable effect on either function. The reduction in net SR Ca2+ uptake: (a) was near-maximal with treatment at 50 mu M Ca2+, (b) was unrelated to voltage-sensor function, and (c) persisted unchanged for > 20 min. The reduction was primarily due to a threefold increase in leakage of Ca2+ out of the SR. This increased leakage was not substantially blocked by the presence of 10 mM Mg2+ or 2 mu M Ruthenium Red.3. The adverse effect on SR function of exposure to high [Ca2+] could also be observed by the reduction in the ability of the SR to maintain a low [Ca2+] within the skinned fibre in the face of elevated [Ca2+] in the bathing solution. When bathed in a solution with similar to 1.5 mu M Ca2+ (0.75 mM CaEGTA-EGTA), skinned fibres produced only low force responses for many minutes, but after high [Ca2+] treatment (15 s exposure to 50 mu M Ca2+) they showed large, steady or oscillatory force responses.4. These findings indicate that, in addition to uncoupling the Ca2+ release channels from the voltage sensors, exposure of skinned fibres to high [Ca2+] causes a persistent increase in resting Ca2+ efflux from the SR. Such efflux in an intact fibre would alter the distribution of Ca2+ between the SR, the cytoplasm and the extracellular solution. These results may be relevant to the basis of low-frequency fatigue and possibly other conditions in muscle.