One of the mechanisms that cells have developed to fulfil their specialized tasks is to express different molecular variants of a particular protein that has unique functional properties. Na,K-ATPase (NKA), the ion transport mechanism that maintains the transmembrane Na⁺ and K⁺ concentrations across the plasma membrane of cells, is one of such protein systems that shows high molecular and functional heterogeneity. Four different isoforms of the NKA catalytic subunit are expressed in mammalian cells (NKAα1, NKAα2, NKAα3, and NKAα4). NKAα4 (ATP1A4) is the isoform with the most restricted pattern of expression, being solely produced in male germ cells of the testis. NKAα4 is abundant in spermatozoa, where it is required for sperm motility and hyperactivation. This review discusses the expression, functional properties, mechanism of action of NKAα4 in sperm physiology, and its role in male fertility. In addition, we describe the use of NKAα4 as a target for male contraception and a potential approach to pharmacologically block its ion transport function to interfere with male fertility.

中文翻译：

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精子的 Na+ 和 K+ 运输系统 (ATP1A4) 对于男性生育能力至关重要，也是男性避孕的一个有吸引力的目标†。


细胞为完成其专门任务而开发的机制之一是表达具有独特功能特性的特定蛋白质的不同分子变体。 Na,K-ATP酶 (NKA) 是一种离子转运机制，可维持细胞质膜上的跨膜 Na ⁺和 K ⁺浓度，是表现出高分子和功能异质性的蛋白质系统之一。 NKA 催化亚基的四种不同亚型在哺乳动物细胞中表达（NKAα1、NKAα2、NKAα3 和 NKAα4）。 NKAα4 (ATP1A4) 是表达模式最受限制的亚型，仅在睾丸的雄性生殖细胞中产生。 NKAα4 在精子中含量丰富，是精子活力和过度活跃所必需的。本文讨论了NKAα4在精子生理学中的表达、功能特性、作用机制及其在男性生育力中的作用。此外，我们描述了使用 NKAα4 作为男性避孕的靶点，以及从药理学上阻断其离子转运功能以干扰男性生育能力的潜在方法。