Conserved Mechanism of Bicarbonate-Induced Sensitization of CatSper Channels in Human and Mouse Sperm.
Conserved Mechanism of Bicarbonate-Induced Sensitization of CatSper Channels in Human and Mouse Sperm.
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碳酸氢盐诱导的人和小鼠精子中catsper通道敏化的保守机制。
DOI：
10.3389/fcell.2021.733653
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发表时间：
2021
影响因子：
5.5
通讯作者：
Santi CM
中科院分区：
文献类型：
--
作者：
Ferreira JJ;Lybaert P;Puga-Molina LC;Santi CM
为了使卵子受精，哺乳动物的精子必须在女性生殖道中经历获能。获能的一个关键因素是钙通道CatSper，该通道由膜去极化和细胞内碱化激活。在小鼠附睾精子中，暴露于高钾环境下的膜去极化仅在碱性条件(pH 8.6)或与碳酸氢盐(HCO3-)和牛血清白蛋白体外孵育(获能条件)后才会触发CatSper的钙离子进入。然而，在射出的人类精子中，膜去极化在非获能条件下以及在低于小鼠精子所需的pH(<；pH 7.4)的情况下通过CatSper触发钙离子进入。在这里，我们的目标是确定在小鼠和人类精子中激活CatSper的机制(S)。我们将射出的小鼠和人类精子暴露在高钾中去极化，发现在pH值为7.4时，这两个物种的精子细胞内钙离子浓度都增加了。相反，在这些条件下，小鼠附睾精子和人附睾精子的细胞内钙离子浓度并没有增加。此外，用HCO3预孵育可引起人附睾精子细胞内钙离子浓度升高，以响应KCl值。在HCO3暴露期间使用蛋白激酶A(PKA)抑制剂可抑制小鼠附睾精子以及小鼠和人射精精子中钙离子浓度的升高。最后，我们发现，人和小鼠精子细胞内钙离子浓度的增加都需要可溶性腺苷环化酶和细胞内pH的升高。综上所述，我们的结果表明，在人类和小鼠精子中都存在一种激活CatSper通道的保守机制。在这一机制中，精液中的HCO3-激活了可溶性的腺苷环化酶/蛋白激酶A途径，导致细胞内pH升高，并使CatSper通道对膜去极化做出反应，从而允许钙离子内流。CatSper敏化的这种间接机制可能是精子一接触精液就发生的早期事件获能。
To fertilize an egg, mammalian sperm must undergo capacitation in the female genital tract. A key contributor to capacitation is the calcium (Ca2+) channel CatSper, which is activated by membrane depolarization and intracellular alkalinization. In mouse epididymal sperm, membrane depolarization by exposure to high KCl triggers Ca2+ entry through CatSper only in alkaline conditions (pH 8.6) or after in vitro incubation with bicarbonate (HCO3–) and bovine serum albumin (capacitating conditions). However, in ejaculated human sperm, membrane depolarization triggers Ca2+ entry through CatSper in non-capacitating conditions and at lower pH (< pH 7.4) than is required in mouse sperm. Here, we aimed to determine the mechanism(s) by which CatSper is activated in mouse and human sperm. We exposed ejaculated mouse and human sperm to high KCl to depolarize the membrane and found that intracellular Ca2+ concentration increased at pH 7.4 in sperm from both species. Conversely, intracellular Ca2+ concentration did not increase under these conditions in mouse epididymal or human epididymal sperm. Furthermore, pre-incubation with HCO3– triggered an intracellular Ca2+ concentration increase in response to KCl in human epididymal sperm. Treatment with protein kinase A (PKA) inhibitors during exposure to HCO3– inhibited Ca2+ concentration increases in mouse epididymal sperm and in both mouse and human ejaculated sperm. Finally, we show that soluble adenylyl cyclase and increased intracellular pH are required for the intracellular Ca2+ concentration increase in both human and mouse sperm. In summary, our results suggest that a conserved mechanism of activation of CatSper channels is present in both human and mouse sperm. In this mechanism, HCO3– in semen activates the soluble adenylyl cyclase/protein kinase A pathway, which leads to increased intracellular pH and sensitizes CatSper channels to respond to membrane depolarization to allow Ca2+ influx. This indirect mechanism of CatSper sensitization might be an early event capacitation that occurs as soon as the sperm contact the semen.
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射精的小鼠精子在体外比附睾精子更有效地进入卵丘-卵母细胞复合体
影响因子：
3.7
作者：
Li H;Hung PH;Suarez SS
通讯作者：
Suarez SS
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
DOI：
10.1073/pnas.2536658100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Carlson, AE;Westenbroek, RE;Babcock, DF
通讯作者：
Babcock, DF
影响因子：
4.1
作者：
Breitbart, H
通讯作者：
Breitbart, H
影响因子：
3.4
作者：
Breitbart, H
通讯作者：
Breitbart, H