MECHANISMS OF LUMINAL ACIDIFICATION IN EPIDYDIMAS & VAS DEFERENS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。活跃的质子转运机制在男性生殖道的排泄管中建立和维持一个腔内酸性环境。低腔内pH值和低碳酸氢盐浓度对于精子成熟，防止顶体酶过早激活，以及在该器官储存期间保持精子处于静止状态是重要的。尽管这一关键功能在男性生殖生理，酸化过程中的男性生殖道仍然不完全了解。我们实验室正在研究参与附睾和输精管腔酸化及其调控的机制。本研究的最终目的是了解有缺陷的酸化如何在病理状态下损害生殖功能，以及如何通过干预来操纵酸化最终可以用来控制男性生育能力。生物电流研究中心开发的非侵入性自我参考质子选择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，我们发现一种对巴非霉素敏感的、空泡式质子泵送的H+- atp酶（v - atp酶）集中在上皮细胞亚群（透明细胞）的顶膜上，是腔内酸化的主要因素。在酸化透明细胞中，质子的分泌是通过含有v - atp酶的囊泡进出质膜的循环来调节的。

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.