The Na+ And K+ Transport System Of Sperm (Atp1a4) Is Essential For Male Fertility And An Attractive Target For Male Contraception

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 (NKA alpha 1, NKA alpha 2, NKA alpha 3, and NKA alpha 4). NKA alpha 4 (ATP1A4) is the isoform with the most restricted pattern of expression, being solely produced in male germ cells of the testis. NKA alpha 4 is abundant in spermatozoa, where it is required for sperm motility and hyperactivation. This review discusses the expression, functional properties, mechanism of action of NKA alpha 4 in sperm physiology, and its role in male fertility. In addition, we describe the use of NKA alpha 4 as a target for male contraception and a potential approach to pharmacologically block its ion transport function to interfere with male fertility.