SLO2.1/NALCN a sodium signaling complex that regulates uterine activity.

SLO2.1/NALCN a sodium signaling complex that regulates uterine activity.
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DOI:
10.1016/j.isci.2021.103210
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发表时间:
2021-11-19
期刊:
影响因子:
5.8
通讯作者:
Santi CM
Santi CM
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Ferreira JJ;Amazu C;Puga-Molina LC;Ma X;England SK;Santi CM

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子宫肌层平滑肌细胞(MSMC)静息膜电位的去极化是子宫从静止状态过渡到收缩状态所必需的。参与这种转变的分子机制尚未完全了解。在这里,我们报告说,钠+激活的K+通道(SLO 2.1)和非选择性Na+泄漏通道(NALCN)之间的耦合系统决定的MSMC膜电位。我们的数据表明,Na+通过NALCN进入作为细胞内信号分子,激活SLO 2.1。通过SLO 2.1的钾流出使膜超极化。SLO2.1/NALCN活性的降低诱导膜去极化,通过电压依赖性Ca 2+通道触发Ca 2+进入并促进收缩。与功能偶联一致,我们的数据显示NALCN和SLO 2.1在人MSMCs中非常接近。我们建议,这些安排的SLO 2.1和NALCN允许这些通道功能调节MSMC膜电位和细胞兴奋性和调节子宫收缩。SLO2.1/NALCN复合物控制子宫兴奋性。SLO 2.1/NALCN活性的降低触发子宫收缩力。生物科学;细胞生理学;细胞生物学;细胞生物学功能方面
Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system between the Na+-activated K+ channel (SLO2.1) and the non-selective Na+ leak channel (NALCN) determines the MSMC membrane potential. Our data indicate that Na+ entering through NALCN acts as an intracellular signaling molecule that activates SLO2.1. Potassium efflux through SLO2.1 hyperpolarizes the membrane. A decrease in SLO2.1/NALCN activity induces membrane depolarization, triggering Ca2+ entry through voltage-dependent Ca2+ channels and promoting contraction. Consistent with functional coupling, our data show that NALCN and SLO2.1 are in close proximity in human MSMCs. We propose that these arrangements of SLO2.1 and NALCN permit these channels to functionally regulate MSMC membrane potential and cell excitability and modulate uterine contractility. The SLO2.1/NALCN complex controls uterine excitability. A decrease in SLO2.1/NALCN activity triggers uterine contractility. Biological sciences; Cellular physiology; Cell biology; Functional aspects of cell biology
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