Membrane phospholipid control of nucleotide sensitivity of KATP channels
Membrane phospholipid control of nucleotide sensitivity of KATP channels
复制标题
DOI：
10.1126/science.282.5391.1138
复制
发表时间：
1998-11-06
期刊：
影响因子：
56.9
通讯作者：
Nichols, CG
中科院分区：
文献类型：
--
作者：
Shyng, SL;Nichols, CG
三磷酸腺苷（ATP）敏感性钾（K-ATP）通道将细胞代谢与电活动偶联。磷脂酰肌醇磷酸盐（PIP）深刻拮抗ATP抑制K-ATP通道时，应用于由内而外的膜补丁。有人提出，膜掺入的pips可以结合到通道的K（ir）6.2亚基的胞质区域中的正电荷，稳定通道的开放状态，并拮抗ATP的抑制作用。PIP对ATP敏感性的巨大影响表明，膜PIP水平的体内改变将对K-ATP通道活性产生实质性影响，从而对代谢-兴奋偶联的增益产生实质性影响。
Adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels couple cell metabolism to electrical activity. Phosphatidylinositol phosphates (PIPs) profoundly antagonized ATP inhibition of K-ATP channels when applied to inside-out membrane patches. It is proposed that membrane-incorporated pips can bind to positive charges in the cytoplasmic region of the channel's K(ir)6.2 subunit, stabilizing the open state of the channel and antagonizing the inhibitory effect of ATP. The tremendous effect of pips on ATP sensitivity suggests that in vivo alterations of membrane PIP levels will have substantial effects on K-ATP channel activity and hence on the gain of metabolism-excitation coupling.