A Model of CatSper Channel Mediated Calcium Dynamics in Mammalian Spermatozoa

CatSpers are calcium (Ca2+) channels that are located along the principal piece of mammalian sperm flagella and are directly linked to sperm motility and hyperactivation. It has been observed that Ca2+ entry through CatSper channels triggers a tail to head Ca2+ propagation in mouse sperm, as well as a sustained increase of Ca2+ in the head. Here, we develop a mathematical model to investigate this propagation and sustained increase in the head. A 1-d reaction-diffusion model tracking intracellular Ca2+ with flux terms for the CatSper channels, a leak flux, and plasma membrane Ca2+ clearance mechanism is studied. Results of this simple model exhibit tail to head Ca2+ propagation, but no sustained increase in the head. Therefore, in this model, a simple plasma membrane pump-leak system with diffusion in the cytosol cannot account for these experimentally observed results. It has been proposed that Ca2+ influx from the CatSper channels induce additional Ca2+ release from an internal store. We test this hypothesis by examining the possible role of Ca2+ release from the redundant nuclear envelope (RNE), an inositol 1,4,5-trisphosphate (IP3) gated Ca2+ store in the neck. The simple model is extended to include an equation for IP3 synthesis, degradation, and diffusion, as well as flux terms for Ca2+ in the RNE. When IP3 and the RNE are accounted for, the results of the model exhibit a tail to head Ca2+ propagation as well as a sustained increase of Ca2+ in the head.