Department of Physiology, University of California, San Francisco, UCSF Mail Code 2140, Genentech Hall, Room N272F, 600 16(th) Street, San Francisco, CA 94158, USA.
Cell. 2010 Feb 5;140(3):327-37. doi: 10.1016/j.cell.2009.12.053.
Human spermatozoa are quiescent in the male reproductive system and must undergo activation once introduced into the female reproductive tract. This process is known to require alkalinization of sperm cytoplasm, but the mechanism responsible for transmembrane proton extrusion has remained unknown because of the inability to measure membrane conductance in human sperm. Here, by successfully patch clamping human spermatozoa, we show that proton channel Hv1 is their dominant proton conductance. Hv1 is confined to the principal piece of the sperm flagellum, where it is expressed at unusually high density. Robust flagellar Hv1-dependent proton conductance is activated by membrane depolarization, an alkaline extracellular environment, endocannabinoid anandamide, and removal of extracellular zinc, a potent Hv1 blocker. Hv1 allows only outward transport of protons and is therefore dedicated to inducing intracellular alkalinization and activating spermatozoa. The importance of Hv1 for sperm activation makes it an attractive target for controlling male fertility.
人类精子在男性生殖系统中处于静止状态，一旦进入女性生殖道，就必须被激活。这个过程需要精子细胞质的碱化，但由于无法测量人类精子的膜电导，因此负责跨膜质子外排的机制仍然未知。在这里，通过成功地对人类精子进行膜片钳实验，我们发现质子通道 Hv1 是其主要的质子电导。Hv1 局限于精子鞭毛的主段，在那里它以异常高的密度表达。强大的鞭毛 Hv1 依赖性质子电导可被膜去极化、碱性细胞外环境、内源性大麻素花生四烯酸酰胺以及去除细胞外锌（强效的 Hv1 阻断剂）激活。Hv1 只允许质子向外转运，因此专门用于诱导细胞内碱化并激活精子。Hv1 对精子激活的重要性使其成为控制男性生育能力的一个有吸引力的靶点。
