Composition and regulation of human sperm potassium channel
Potassium (K+) channels play a critical role in regulating membrane potential via K+ efflux leading to hyperpolarization which is essential for sperm maturation and successful fertilization1-3. Although the principal K+ channel in human sperm, KSper, is essential for sperm function4, its full molecular identity has yet to be elucidated. Interestingly, human KSper is activated by intracellular calcium, which makes it different from mouse KSper5-7. The latter is represented by Slo3 and is a pH-sensitive and calcium-insensitive channel7. While human sperm cells also express Slo3 channel5, as well as calcium-sensitive K+ channel Slo16, their physiological and pharmacological properties do not fully match either Slo3 or Slo1 alone, suggesting a unique composition of the channel complex.
- Zeng, X. H., Yang, C., Kim, S. T., Lingle, C. J. & Xia, X. M. Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa. Proc Natl Acad Sci USA 108, 5879-5884 (2011).
- Santi, C. M. et al. The SLO3 sperm-specific potassium channel plays a vital role in male fertility. FEBS Lett 584, 1041-1046 (2010).
- Schreiber, M. et al. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J Biol Chem 273, 3509-3516 (1998).
- Brown, S. G. et al. Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF. Hum Reprod 31, 1147-1157 (2016).
- Brenker, C. et al. The Ca2+-activated K+ current of human sperm is mediated by Slo3. eLife 3, e01438 (2014).
- Mannowetz, N., Naidoo, N. M., Choo, S. A., Smith, J. F. & Lishko, P. V. Slo1 is the principal potassium channel of human spermatozoa. eLife 2, e01009 (2013).
- Navarro, B., Kirichok, Y. & Clapham, D. E. KSper, a pH-sensitive K+ current that controls sperm membrane potential. Proc Natl Acad Sci U S A 104, 7688-7692 (2007).