期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：12
DOI：10.1073/pnas.2114046119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P
2) levels regulate cell membrane voltage by gluing two halves of a K
+ channel together and opening the pore. PI(4)P competes with this process. Because both of these lipids are relatively abundant in the plasma membrane and are directly interconvertible through the action of specific enzymes, they may function together to regulate channel activity.
Inward rectifier K
+(Kir) channels regulate cell membrane potential. Different Kir channels respond to unique ligands, but all are regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P
2). Using planar lipid bilayers, we show that Kir2.2 exhibits bursts of openings separated by long quiescent interburst periods. Increasing PI(4,5)P
2 concentration shortens the Kir2.2 interburst duration and lengthens the burst duration without affecting dwell times within a burst. From this, we propose that burst and interburst durations correspond to the cytoplasmic domain (CTD)–docked and CTD-undocked conformations observed in the presence and absence of PI(4,5)P
2 in atomic structures. We also studied the effect of different phosphatidylinositol lipids on Kir2.2 activation and conclude that the 5′ phosphate is essential to Kir2.2 pore opening. Other phosphatidylinositol lipids can compete with PI(4,5)P
2 but cannot activate Kir2.2 without the 5′ phosphate. PI(4)P, which is directly interconvertible to and from PI(4,5)P
2, might thus be a regulator of Kir channels in the plasma membrane.
