Na(+)/H(+) Exchangers Involve in Regulating the pH-Sensitive Ion Channels in Mouse Sperm.
Na(+)/H(+) Exchangers Involve in Regulating the pH-Sensitive Ion Channels in Mouse Sperm.
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Na /H 交换剂参与调节小鼠精子中 pH 敏感的离子通道
DOI：
10.3390/ijms22041612
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发表时间：
2021-02-05
影响因子：
5.6
通讯作者：
Zeng XH
中科院分区：
文献类型：
--
作者：
Kang H;Liu M;Zhang W;Huang RZ;Zhao N;Chen C;Zeng XH
精子特异性K+离子通道（KSper）和Ca 2+离子通道（CatSper）分别决定膜电位和Ca 2+内流，其消除导致小鼠雄性不育。KSper和CatSper可以通过细胞溶质碱化激活，这发生在精子通过雌性生殖道的碱性环境期间。然而，细胞内pH值（pHi）调节功能耦合到激活KSper/CatSper仍然不清楚。虽然Na+/H+交换剂（NHE）已被认为介导精子中的pHi，但缺乏直接证据证实NHE与KSper/CatSper之间的功能偶联。本文选择了一种NHEs抑制剂5-（N，N-二甲基）-阿米洛利（DMA）来研究NHEs对小鼠精子中KSper/CatSper的作用。膜片钳记录的结果表明，当细胞外的pH值为7.4的生理水平，DMA的应用引起KSper抑制和去极化的膜电位时，移液管溶液没有pH缓冲。相反，当移液器溶液为pH缓冲时，这些影响最小化，表明它们仅由NHE抑制引起的pH酸化引起。类似地，DMA处理降低CatSper电流和细胞内Ca 2+，效果也依赖于移液管溶液中pH的缓冲能力。DMA孵育后精子活力也明显降低。这些结果表明，在生理条件下，NHEs活性与KSper/CatSper的活化偶联。
Sperm-specific K+ ion channel (KSper) and Ca2+ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca2+ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through the alkaline environment of the female reproductive tract. However, which intracellular pH (pHi) regulator functionally couples to the activation of KSper/CatSper remains obscure. Although Na+/H+ exchangers (NHEs) have been implicated to mediate pHi in sperm, there is a lack of direct evidence confirming the functional coupling between NHEs and KSper/CatSper. Here, 5-(N,N-dimethyl)-amiloride (DMA), an NHEs inhibitor that firstly proved not to affect KSper/CatSper directly, was chosen to examine NHEs function on KSper/CatSper in mouse sperm. The results of patch clamping recordings showed that, when extracellular pH was at the physiological level of 7.4, DMA application caused KSper inhibition and the depolarization of membrane potential when pipette solutions were not pH-buffered. In contrast, these effects were minimized when pipette solutions were pH-buffered, indicating that they solely resulted from pHi acidification caused by NHEs inhibition. Similarly, DMA treatment reduced CatSper current and intracellular Ca2+, effects also dependent on the buffer capacity of pH in pipette solutions. The impairment of sperm motility was also observed after DMA incubation. These results manifested that NHEs activity is coupled to the activation of KSper/CatSper under physiological conditions.
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影响因子：
9
作者：
Chen SR;Chen M;Deng SL;Hao XX;Wang XX;Liu YX
通讯作者：
Liu YX
影响因子：
3.8
作者：
Muzzachi, Stefania;Guerra, Lorenzo;Ciani, Elena
通讯作者：
Ciani, Elena
影响因子：
64.5
作者：
Hwang JY;Mannowetz N;Zhang Y;Everley RA;Gygi SP;Bewersdorf J;Lishko PV;Chung JJ
通讯作者：
Chung JJ
影响因子：
4.8
作者：
Oberheide, Karina;Puchkov, Dmytro;Jentsch, Thomas J.
通讯作者：
Jentsch, Thomas J.
DOI：
10.2741/e115
发表时间：
2010-01-01
期刊：
Frontiers in bioscience (Elite edition)
影响因子：
--
作者：
Liu, Tao;Huang, Jun-Cheng;Liu, Yi-Xun
通讯作者：
Liu, Yi-Xun