Spotlight on the Binding Affinity of Ion Channels for Phosphoinositides: From the Study of Sperm Flagellum

The previous studies revealed that many types of ion channels have sensitivity to PtdIns(4,5)P₂, which has been mainly shown using heterologous expression system. On the other hand, there remains few evidence showing that PtdIns(4,5)P₂ natively regulate the ion channel activities in physiological context. Our group recently discovered that a sperm specific K⁺ channel, Slo3, is natively regulated by PtdIns(4,5)P₂ in sperm flagellum. Very interestingly, a principal piece, to which Slo3 specifically localized, had extremely low density of PtdIns(4,5)P₂ compared to the regular cell plasma membrane. Furthermore, our studies and the previous ones also revealed that Slo3 had much stronger PtdIns(4,5)P₂ affinity than KCNQ2/3 channels, which are widely regulated by endogenous PtdIns(4,5)P₂ in neurons. Thus, the high-PtdIns(4,5)P₂ affinity of Slo3 is well-adapted to the specialized PtdIns(4,5)P₂ environment in the principal piece. This study sheds light on the relationship between PtdIns(4,5)P₂-affinity of ion channels and their PtdIns(4,5)P₂ environment in native cells. We discuss the current understanding about PtdIns(4,5)P₂ affinity of diverse ion channels and their possible regulatory mechanism in native cellular environment.