MECHANISMS OF LUMINAL ACIDIFICATION IN EPIDYDIMAS & VAS DEFERENS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 主动质子转运机制在雄性生殖道的流出道中建立并维持一个腔酸性环境。低内腔pH和低碳酸氢盐浓度对于精子成熟、防止顶体酶过早激活以及在该器官中储存期间维持精子处于静止状态是重要的。尽管这在男性生殖生理学中具有重要作用，但男性生殖道中的酸化过程仍不完全清楚。我们的实验室正在研究参与腔酸化及其在附睾和输精管中的调节的机制。本研究的最终目标是了解在病理状态下，有缺陷的酸化如何损害生殖功能，以及如何干预操纵酸化最终可用于控制男性生育力。 BioCurrrents研究中心开发的非侵入性自参考质子选择性微电极使我们能够确定输精管初始部分的主要质子分泌机制。在与Peter Smith的合作中，我们已经表明，巴非霉素敏感的空泡质子泵H+-ATP酶（V-ATP酶）集中在上皮细胞（透明细胞）亚群的顶膜中，并且是管腔酸化的主要贡献者。在酸化透明细胞中，质子分泌通过含有V-ATP酶的囊泡往返质膜的再循环来调节。 .

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Active proton transport mechanisms establish and maintain a luminal acidic environment in the excurrent ducts of the male reproductive tract. The low luminal pH and a low bicarbonate concentration are important for sperm maturation, the prevention of premature activation of acrosomal enzymes, and for maintaining sperm in a quiescent state during storage in this organ. Despite this critical function in male reproductive physiology, acidification processes in the male reproductive tract are still incompletely understood. Our laboratory is studying the mechanisms that participate in luminal acidification and its regulation in the epididymis and vas deferens. The ultimate goals of this study are to understand how defective acidification may impair reproductive function in pathologic states, and how intervention to manipulate acidification may eventually be used to control male fertility. The non-invasive self-referencing proton-selective micro electrode developed in the BioCurrrents Research Center has allowed us to identify the major proton secretory mechanism in the initial part of the vas deferens. In collaboration with Peter Smith, we have shown that a bafilomycin-sensitive, vacuolar proton-pumping H+-ATPase (V-ATPase) is concentrated in the apical membrane of a subpopulation of epithelial cells (clear cells) and is a major contributor to luminal acidification. In acidifying clear cells, proton secretion is regulated via recycling of V-ATPase-containing vesicles to and from the plasma membrane. .