先前的研究表明,许多类型的离子通道对PtdIns(4,5)P2具有敏感性,这主要是使用异源表达系统显示的。另一方面,仍然没有证据表明PtdIns(4,5)P2在生理环境中天然调节离子通道活性。我们小组最近发现了一种精子特异性K+通道,Slo3由精子鞭毛中的PtdIns(4,5)P2天然调节。非常有趣的是,一个主要的作品,Slo3专门定位的地方,与常规细胞质膜相比,PtdIns(4,5)P2的密度极低。此外,我们的研究和以前的研究还表明,Slo3比KCNQ2/3通道具有更强的PtdIns(4,5)P2亲和力,它们在神经元中受到内源性PtdIns(4,5)P2的广泛调节。因此,Slo3的高PtdIns(4,5)P2亲和力非常适合主要作品中的专用PtdIns(4,5)P2环境。本研究揭示了天然细胞中离子通道的PtdIns(4,5)P2亲和力与其PtdIns(4,5)P2环境之间的关系。我们讨论了目前对不同离子通道的PtdIns(4,5)P2亲和力及其在天然细胞环境中可能的调节机制的理解。
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.