The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception

Shameem Sultana Syeda, Gladis Sánchez, Jeffrey P. McDermott, Kwon Ho Hong, Gustavo Blanco, Gunda I. Georg

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)343-356
Number of pages14
JournalBiology of reproduction
Issue number2
StatePublished - Aug 4 2020

Bibliographical note

Funding Information:
This work was supported by the Contraception Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development through U01HD080423 (GB) and contract HHSN275201300017C (GIG).

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. Reproduction. All rights reserved. For permissions, please e-mail:


  • Male fertility
  • Ouabain
  • Sperm capacitation
  • Sperm hypermotility
  • Sperm motility

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Review


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