Na+-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition.
Na+-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition.
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DOI：
10.1159/000491805
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发表时间：
2018
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影响因子：
--
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--
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子宫收缩力由子宫肌层平滑肌细胞产生的电信号控制。由于异常的电信号可能导致子宫收缩效率低下和生殖结果不良，因此对确定调节子宫兴奋性的离子通道有很大的兴趣。在人子宫肌层中，Na+泄漏通道，非选择性（NALCN）有助于钆敏感性、Na+依赖性泄漏电流。本研究的目的是确定NALCN在调节子宫兴奋性中的作用，并检查其在分娩中的参与。野生型C57 BL/6 J小鼠进行定时交配，并在整个妊娠期间的几个时间点（包括妊娠第7、10、14、18和19天）测量NALCN子宫表达。在这些相同的时间点，使用锋利电极电流钳测量子宫兴奋性。为了确定NALCN对子宫肌层兴奋性和妊娠结局的贡献，我们通过将NALCNfx/fx小鼠与肌球蛋白重链Cre（MHCCre-eGFP）小鼠杂交来创建平滑肌特异性NALCN敲除小鼠。通过监测录像记录cre对照、flox对照、smNALCN+/−和smNALCN−/−小鼠的分娩结局，评估分娩结局。比较妊娠第19天flox对照组和smNALCN−/−小鼠的子宫肌层兴奋性。我们发现，在小鼠子宫中，NALCN蛋白水平在妊娠早期较高，在妊娠中期和晚期下降，然后在分娩和产后增加。尖锐电极电流钳记录的小鼠纵向子宫肌层样品从怀孕第7，10，14，18，和19天显示，爆发持续时间和间隔的日依赖性增加，尖峰密度下降。NALCN平滑肌基因敲除小鼠子宫肌层兴奋性降低，表现为动作电位爆发缩短，异常分娩率增加，包括分娩时间延长和功能障碍。总之，我们的研究结果表明，Na+传导通道NALCN有助于子宫肌层动作电位波形，对成功的分娩结局很重要。
Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCre-eGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/−, and smNALCN−/− mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN−/− mice. We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes.
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影响因子：
2.5
作者：
Floyd RV;Mobasheri A;Wray S
通讯作者：
Wray S
影响因子：
7.7
作者：
Lutas, Andrew;Lahmann, Carolina;Yellen, Gary
通讯作者：
Yellen, Gary
影响因子：
3.8
作者：
KLEINHAUS, AL;KAO, CY
通讯作者：
KAO, CY
影响因子：
4.5
作者：
Miyoshi, H;Yamaoka, K;Ohama, K
通讯作者：
Ohama, K
DOI：
10.3791/4389
发表时间：
2012-09-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
McLean AC;Valenzuela N;Fai S;Bennett SA
通讯作者：
Bennett SA