Store-operated Ca2+ entry is activated by every action potential in skeletal muscle
Store-operated Ca2+ entry is activated by every action potential in skeletal muscle
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DOI：
10.1038/s42003-018-0033-7
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发表时间：
2018-01-01
影响因子：
5.9
通讯作者：
Launikonis, Bradley S.
中科院分区：
文献类型：
--
作者：
Koenig, Xaver;Choi, Rocky H.;Launikonis, Bradley S.
在直接激活 Ca2+ 释放过程中，骨骼肌中钙库操纵的钙 (Ca2+) 进入 (SOCE) 会在整个管状系统中快速激活。管状系统是质膜的内陷，与肌浆网 (SR) 形成连接，STIM1、Orai1 和兰尼碱受体位于此处。肌肉中 SOCE 的生理激活尚未明确，因此模糊了其生理作用。在这里，我们表明阶段性肾小管系统 Ca2+ 流入的幅度取决于 SR Ca2+ 消耗的幅度，并将其定义为 SOCE。与 SOCE 一致，流入对硝苯地平和 BayK8644 具有抗性，并通过在兴奋期间抑制 SR Ca2+ 释放而沉默。 SOCE 瞬态由动作电位频率和 SR Ca2+ 泵活动决定。我们的结果表明，在兴奋-收缩耦合过程中，骨骼肌中的 SOCE 可以立即抵消肾小管系统中 Ca2+ 的损失。
Store-operated calcium (Ca2+) entry (SOCE) in skeletal muscle is rapidly activated across the tubular system during direct activation of Ca2+ release. The tubular system is the invagination of the plasma membrane that forms junctions with the sarcoplasmic reticulum (SR) where STIM1, Orai1 and ryanodine receptors are found. The physiological activation of SOCE in muscle is not defined, thus clouding its physiological role. Here we show that the magnitude of a phasic tubular system Ca2+ influx is dependent on SR Ca2+ depletion magnitude, and define this as SOCE. Consistent with SOCE, the influx was resistant to nifedipine and BayK8644, and silenced by inhibition of SR Ca2+ release during excitation. The SOCE transient was shaped by action potential frequency and SR Ca2+ pump activity. Our results show that SOCE in skeletal muscle acts as an immediate counter-flux to Ca2+ loss across the tubular system during excitation-contraction coupling.