Figure 3. Spermatozoa ion channel activation and regulation integrated model.

HCO₃⁻ ions bind and activate soluble adenylyl cyclase (sAC) that in turn increases cAMP synthesis. cAMP activates (direct or indirectly) the sperm specific Na⁺/H⁺ exchange (sNHE), thereby increasing intracellular pH. This intracellular alkalinization potently increases I_CatSper and I_KSper. Alkalinization-mediated potentiation of I_KSper hyperpolarizes the membrane potential from ~0 to ~ −50 mV. Ca²⁺ entry through I_CatSper induces a rise in [Ca²⁺]_I, in turn activating Calmodulin and Calmodulin Kinase (CamK). These changes increase flagellar bending and enhance ATP production, thus increasing sperm endurance and hyperactivating sperm motility. Images of normal and hyperactivated motile sperm modified after Carlson, et al., 2005.