Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa.
Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa.
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同时敲除 Slo3 和 CatSper1 可消除小鼠精子中的所有碱化激活电流和电压激活电流
DOI：
10.1085/jgp.201311011
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Lingle CJ
中科院分区：
文献类型：
--
作者：
Zeng XH;Navarro B;Xia XM;Clapham DE;Lingle CJ
在通过女性生殖道期间，哺乳动物精子经历称为获能的成熟过程，使精子有能力产生受精。获能涉及生化和电特性的一系列变化、过度活跃的游泳行为的开始以及与卵子成功融合和穿透的能力的发展。在小鼠精子中，过度活跃运动的发展依赖于胞质碱化，从而导致胞质 Ca2+ 增加。 Ca2+ 的升高被认为主要是由两种碱化激活电流的协同相互作用驱动的，即由 Kcnu1 基因（也称为 Slo3）编码的成孔亚基组成的 K+ 电流 (KSPER) 和由 CATSPER 亚基家族产生的 Ca2+ 电流。删除四个 CATSPER 亚基基因 (CATSPER1-4) 中的任何一个后，小鼠精子中剩余的主要电流是碱化激活的 KSPER 电流。 Slo3 基因基因删除后，KSPER 电流被消除，但仍然存在一个小的电压激活 K+ 电流，假设反映通过 CATSPER 的单价通量。在这里，我们解决两个问题。首先，Slo3 −/− 精子中存在的残留外向 K+ 电流是否来自 CATSPER？其次，除了 CATSPER 和 KSPER 之外，还可以通过膜片钳方法检测小鼠精子中任何额外的膜 K+ 电流吗？在这里，我们使用缺乏 SLO3 和 CATSPER1 亚基的小鼠，最终证明，当 CATSPER 也被删除时，Slo3 −/− 精子中存在的电压激活的外向电流被消除。任何可能在设置非获能精子的静息膜电位方面发挥作用的漏电流可能小于移液管漏电流，因此无法在膜片钳技术的限制内解决。 KSPER 和 CATSPER 似乎是小鼠精子中存在的唯一离子通道，可调节膜电位和 Ca2+ 内流以响应碱化。
During passage through the female reproductive tract, mammalian sperm undergo a maturation process termed capacitation that renders sperm competent to produce fertilization. Capacitation involves a sequence of changes in biochemical and electrical properties, the onset of a hyperactivated swimming behavior, and development of the ability to undergo successful fusion and penetration with an egg. In mouse sperm, the development of hyperactivated motility is dependent on cytosolic alkalization that then results in an increase in cytosolic Ca2+. The elevation of Ca2+ is thought to be primarily driven by the concerted interplay of two alkalization-activated currents, a K+ current (KSPER) composed of pore-forming subunits encoded by the Kcnu1 gene (also termed Slo3) and a Ca2+ current arising from a family of CATSPER subunits. After deletion of any of four CATSPER subunit genes (CATSPER1–4), the major remaining current in mouse sperm is alkalization-activated KSPER current. After genetic deletion of the Slo3 gene, KSPER current is abolished, but there remains a small voltage-activated K+ current hypothesized to reflect monovalent flux through CATSPER. Here, we address two questions. First, does the residual outward K+ current present in the Slo3 −/− sperm arise from CATSPER? Second, can any additional membrane K+ currents be detected in mouse sperm by patch-clamp methods other than CATSPER and KSPER? Here, using mice bred to lack both SLO3 and CATSPER1 subunits, we show conclusively that the voltage-activated outward current present in Slo3 −/− sperm is abolished when CATSPER is also deleted. Any leak currents that may play a role in setting the resting membrane potential in noncapacitated sperm are likely smaller than the pipette leak current and thus cannot be resolved within the limitation of the patch-clamp technique. Together, KSPER and CATSPER appear to be the sole ion channels present in mouse sperm that regulate membrane potential and Ca2+ influx in response to alkalization.
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DOI：
10.1085/jgp.88.3.293
发表时间：
1986-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hess P;Lansman JB;Tsien RW
通讯作者：
Tsien RW
影响因子：
0.7
作者：
Navarro, Betsy;Kirichok, Yuriy;Clapham, David E.
通讯作者：
Clapham, David E.
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
DOI：
10.1073/pnas.0610286104
发表时间：
2007-01-23
影响因子：
11.1
作者：
Qi, Huayu;Moran, Magdalene M.;Clapham, David E.
通讯作者：
Clapham, David E.
影响因子：
16.6
作者：
Chung JJ;Navarro B;Krapivinsky G;Krapivinsky L;Clapham DE
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