Proposed model for fertilization signaled activation of TMEM16A. Before fertilization, X. laevis eggs have a negative resting potential, thereby electrically signaling to sperm that they can receive a male gamete. After fertilization, cytosolic Ca²⁺ increases to activate TMEM16Aa. An efflux of Cl⁻ then depolarizes the egg, and this change in membrane potential blocks supernumerary sperm from entering the fertilized egg.