Model for the fast polyspermy block in X. laevis. In the fast block to polyspermy in X. laevis eggs, fertilization activates a PLC, which then cleaves PIP₂ to create IP₃. This increased IP₃ then activates its cognate receptor on the ER to evoke a Ca²⁺ release. This ER-derived Ca²⁺ then activates a Cl⁻ channel, which conducts a Cl⁻ efflux to depolarize the egg. Research described in the companion paper (Wozniak et al., 2018) identifies this Cl⁻ channel as TMEM16A. This fertilization-signaled depolarization prevents sperm entry into an already-fertilized egg.