To fertilize an egg, human sperm must undergo a process in which the membrane becomes more negative inside. The ion channel responsible for this membrane hyperpolarization has long been unclear. In this publication, the Santi and Denton labs describe a screen to identify inhibitors of a strong candidate – the sperm-specific potassium channel SLO3. They discovered the first highly selective inhibitor of this channel and they used it to show that SLO3 is responsible for human sperm hyperpolarization. Additionally, inhibiting SLO3 with this compound significantly impaired sperm function. This work may improve our understanding of some cases of unexplained male infertility and lead to the development of new contraceptives.
Max Lyon, PhD student, Ping Li, Senior Scientist are the first co-authors of the paper with Juan Ferreira, PhD.