Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel
Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel
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DOI：
10.1038/nature04417
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发表时间：
2006-02-09
期刊：
影响因子：
64.8
通讯作者：
Clapham, DE
中科院分区：
文献类型：
--
作者：
Kirichok, Y;Navarro, B;Clapham, DE
在哺乳动物中，精子细胞在射精过程中变得能动，并沿着雌性生殖道向上游动。在受精之前，为了克服各种障碍，它们的运动必须被过度激活，这种运动的特征是强烈的不对称尾巴跳动（1）。超激活需要鞭毛中钙的增加，这一过程可能涉及质膜离子通道（2 - 8）。在过去的二十年里，许多试图了解精子细胞通道的尝试都因测量精子跨膜离子电流的困难而受挫（2，3，9 - 16）。在这里，通过使用一个简单的方法来膜片钳精子和整个精子电流的特点，我们描述了一个组成性的活性鞭毛钙通道，强烈增强细胞内碱化。这种电流不存在于缺乏精子特异性推定离子通道蛋白CatSper1的精子中。六跨膜离子通道超家族的这种质膜蛋白特异性定位于精子尾部的主要部分，并且是精子细胞超活化和男性生育力所需的（4，5）。我们的研究结果确定CatSper 1作为一个关键的鞭毛钙通道的组成部分，并建议细胞内碱化增强CatSper电流，以增加鞭毛内钙离子和诱导精子超活化。
In mammals, sperm cells become motile during ejaculation and swim up the female reproductive tract. Before fertilization and to overcome various barriers, their motility must be hyperactivated, a motion that is characterized by vigorous asymmetric tail beating(1). Hyperactivation requires an increase in calcium in the flagella, a process that probably involves plasmalemmal ion channels(2-8). Numerous attempts in the past two decades to understand sperm cell channels have been frustrated by the difficulty of measuring spermatozoan transmembrane ion currents(2,3,9 - 16). Here, by using a simple approach to patch-clamp spermatozoa and to characterize whole-spermatozoan currents, we describe a constitutively active flagellar calcium channel that is strongly potentiated by intracellular alkalinization. This current is not present in spermatozoa lacking the sperm-specific putative ion channel protein, CatSper1. This plasma membrane protein of the six transmembrane-spanning ion channel superfamily is specifically localized to the principal piece of the sperm tail and is required for sperm cell hyperactivation and male fertility(4,5). Our results identify CatSper1 as a component of the key flagellar calcium channel, and suggest that intracellular alkalinization potentiates CatSper current to increase intraflagellar calcium and induce sperm hyperactivation.