Slo3钾通道和CatSper钙通道是精子特异性、pH敏感的两种重要离子通道。申请人前期研究表明（PNAS，2011a，2011b），Slo3 是控制小鼠精子生育力的关键钾离子通道。然而，有关Slo3在人精子中的特性和功能的了解几乎是空白。申请人拟结合hSlo3的异体生物物理研究、在体电生理研究、以及传统生殖学方法等，揭示hSlo3的特性和可能的生理功能。更进一步，通过比较正常和某些不育症患者精子细胞上hSlo3和CatSper表达和特性的差异，以期揭示精子特异性离子通道表达和功能异常与男性不育的内在联系。同时，申请人将探讨上述关键离子通道和精子上pH调控转运体之间的耦联机制。本课题的完成对深入认识精子生理、诊疗男性不育和开发新型避孕药具有重要意义。申请人和合作者的相关工作已发表在Nature, NSB, PNAS, JN, JGP，JP，PLoS One等杂志上。

Both Slo3 potassium channel and CatSper calcium channel are sperm-specific,alkalization-activated ion channels important for mammalian sperm function. The applicant's previous reports (PNAS,2011a,2011b) have demonstrated that Slo3 is the dominant potassium channel in mouse sperm to regulate male fertility, and the deletion of Slo3 gene results in infertility in male mice. However, barely is it known regarding the in vivo expression, biophysical properties and physiological functions of human Slo3. By combining biophysical studies on heterologously expressed hSlo3 and electrophysiological studies in human sperm with traditional in vitro fertilization methods, this project aims to reveal the properties and possible functions of Slo3 in human sperm. Furthermore,taking advantage of the applicant's unique techniques of completing electrophysiological research directly in sperm, by comparing the expression level and functional differences between normal sperm and sperm from infertile men, this project is also anticipated to illustrate the intrinsic relationship between ion channel disorder and male infertility. On the other hand, we will examine the coupling mechanisms between the above critical ion channels and pH regulatory transporters in sperm. Overall, the success of this project will systematically reveal the physiological and pathological roles of ion channels in human sperm, forming basis for developing creative diagnosis and treatment methods for male infertility or screening novel male contraceptives.The applicant and co-applicant have extended research experience in the related field with publications in a series of prestigious journals.