Molecular mechanisms of mammalian sperm capacitation, and its regulation by sodium-dependent secondary active transporters.

Background: Mammalian spermatozoa have to be "capacitated" to be fertilization-competent. Capacitation is a collective term for the physiological and biochemical changes in spermatozoa that occur within the female body. However, the regulatory mechanisms underlying capacitation have not been fully elucidated.

Methods: Previously published papers on capacitation, especially from the perspective of ions/channels/transporters, were extracted and summarized.

Results: Capacitation can be divided into two processes: earlier events (membrane potential hyperpolarization, intracellular pH rise, intracellular Ca²⁺ rise, etc.) and two major later events: hyperactivation and the acrosome reaction. Earlier events are closely interconnected with each other. Various channels/transporters are involved in the regulation of them, which ultimately lead to the later events. Manipulating the extracellular K⁺ concentration based on the oviductal concentration modifies membrane potential; however, the later events and fertilization are not affected, suggesting the uninvolvement of membrane potential in capacitation. Hyperpolarization is a highly conserved phenomenon among mammalian species, indicating its importance in capacitation. Therefore, the physiological importance of hyperpolarization apart from membrane potential is suggested.

Conclusion: The hypotheses are (1) hyperpolarizing Na⁺ dynamics (decrease in intracellular Na⁺) and Na⁺-driven secondary active transporters play a vital role in capacitation and (2) the sperm-specific potassium channel Slo3 is involved in volume and/or morphological regulation.