Abstract:
The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K+ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H+ (pHi) and extracellular K+ concentration [K+]o, and hence provides a link between pHi and [K+]o changes and membrane potential. The intrinsic pHi sensitivity of Kir5.1 suggests a possible role for this channel in the pHi-dependent processes that take place during fertilization. However, despite the localization of Kir5.1 in murine spermatozoa, and its increased expression with age and sexual maturity, the role of the channel in sperm morphology, maturity, motility, and fertility is unknown. Here, we confirmed the presence of Kir5.1 in spermatozoa and showed strong expression of Kir4.1 channels in smooth muscle and epithelial cells lining the epididymal ducts. In contrast, Kir4.2 expression was not detected in testes. To examine the possible role of Kir5.1 in sperm physiology, we bred mice with a deletion of the Kcnj16 (Kir5.1) gene and observed that 20% of Kir5.1 knock-out male mice were infertile. Furthermore, 50% of knock-out mice older than 3 months were unable to breed. By contrast, 100% of wild-type (WT) mice were fertile. The genetic inactivation of Kcnj16 also resulted in smaller testes and a greater percentage of sperm with folded flagellum compared to WT littermates. Nevertheless, the abnormal sperm from mutant animals displayed increased progressive motility. Thus, ablation of the Kcnj16 gene identifies Kir5.1 channel as an important element contributing to testis development, sperm flagellar morphology, motility, and fertility. These findings are potentially relevant to the understanding of the complex pHi- and [K+]o-dependent interplay between different sperm ion channels, and provide insight into their role in fertilization and infertility.
摘要:
精子向卵母细胞游动并使其受精的能力取决于精确的K通透性变化。Kir5.1是一种向内整流钾(Kir)通道,对细胞内H(pHi)和细胞外K浓度[K]o具有很高的敏感性,因此提供了pHi和[K+]o变化和膜电位之间的联系。Kir5.1的固有pHi敏感性表明该通道在受精过程中发生的pHi依赖性过程中可能发挥作用。然而,尽管Kir5.1在小鼠精子中定位,它的表达随着年龄和性成熟而增加,通道在精子形态中的作用,成熟,运动性,生育能力是未知的。这里,我们证实了精子中Kir5.1的存在,并在附睾管衬里的平滑肌和上皮细胞中显示出Kir4.1通道的强表达。相比之下,在睾丸中未检测到Kir4.2表达。为了检查Kir5.1在精子生理中的可能作用,我们饲养了Kcnj16(Kir5.1)基因缺失的小鼠,观察到20%的Kir5.1敲除雄性小鼠不育。此外,超过3个月的敲除小鼠中有50%无法繁殖。相比之下,100%的野生型(WT)小鼠是可育的。与WT同窝动物相比,Kcnj16的遗传失活还导致睾丸更小,鞭毛折叠的精子百分比更高。然而,来自突变动物的异常精子表现出增加的进行性运动性。因此,Kcnj16基因的消融将Kir5.1通道识别为有助于睾丸发育的重要元素,精子鞭毛形态,运动性,和生育能力。这些发现可能与理解不同精子离子通道之间复杂的phi和[K]o依赖性相互作用有关,并深入了解它们在受精和不育中的作用。