Modulation of intrasperm Ca 2+ : A possible maneuver for spermicidal activity

• Published in: Drug development research 2005-05, Vol.65 (1), p.1-16
• Main Authors: Gupta, Anshu, Gupta, Puneet Kumar, Jain, Subheet, Moudgil, Pranab, Tiwary, Ashok Kumar
• Format: Article
• Language: English
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.20006

Sperm in the testis and proximal part of epididymis are nonmotile. As sperm matures, its response towards Ca 2+ changes. The cation is essential for stimulating motility of sperm in epididymis. However, both a decrease in extracellular Ca 2+ below 65% and an increase in the intracellular Ca 2+ above 1200 nM are detrimental to sperm survival in ejaculated semen. Ca 2+ homeostasis in sperm cells is intricately maintained through influx and efflux of Ca 2+ via various channels and pumps present on sperm membrane. Depletion of intracellular calcium evokes the opening of calcium channels present on sperm, thus causing Ca 2+ influx. The efflux of Ca 2+ can be effectively blocked by Na + ‐Ca 2+ exchange inhibitors, thus resulting in elevation of intracellular Ca 2+ beyond the threshold level. Na + ‐K + ‐ATPase inhibitors and IP3 modulators can potentiate this effect. Furthermore, Ca 2+ channel blockers acting on L‐ and T‐type channels can modulate intrasperm Ca 2+ by influencing its influx. In addition, a close relationship exists between Ca 2+ and other regulators of sperm viability such as intracellular pH (Na + ‐H + exchanger), cAMP, protein kinases, calmodulin, etc. In light of these facts, it becomes imperative to consider the pivotal role of intracellular Ca 2+ in sperm function and to critically evaluate the possible use of pharmacological agents as contact spermicides. This should aid in identifying novel target sites for arresting sperm viability in ejaculated human semen. As these agents will act on ejaculated sperm, they should be devoid of any adverse effects associated with the other contraceptives. The ideal agent will be one that acts selectively on a sperm Ca 2+ mobilization process or preferably on a Ca 2+ mobilization process that is expressed only in sperm. Recent reports on Catsper, a cation channel expressed only in sperm cells, have generated considerable interest in the search for novel nonhormonal approaches for contraception. Drug Dev. Res. 65:1–16, 2005. © 2005 Wiley‐Liss, Inc.