Hilgemann D W
University of Texas Southwestern, Medical Center at Dallas 75235-9040, USA.
Annu Rev Physiol. 1997;59:193-220. doi: 10.1146/annurev.physiol.59.1.193.
Many ion transporters and channels appear to be regulated by ATP-dependent mechanisms when studied in planar bilayers, excised membrane patches, or with whole-cell patch clamp. Protein kinases are obvious candidates to mediate ATP effects, but other mechanisms are also implicated. They include lipid kinases with the generation of phosphatidylinositol phosphates as second messengers, allosteric effects of ATP binding, changes of actin cytoskeleton, and ATP-dependent phospholipases. Phosphatidylinositol-4,5-bisphosphate (PIP2) is a possible membrane-delimited messenger that activates cardiac sodium-calcium exchange, KATP potassium channels, and other inward rectifier potassium channels. Regulation of PIP2 by phospholipase C, lipid phosphatases, and lipid kinases would thus tie surface membrane transport to phosphatidylinositol signaling. Sodium-hydrogen exchange is activated by ATP through a phosphorylation-independent mechanism, whereas ion cotransporters are activated by several protein kinase mechanisms. Ion transport in epithelium may be particularly sensitive to changes of cytoskeleton that are regulated by ATP-dependent cell signaling mechanisms.
当在平面双层膜、切除的膜片或采用全细胞膜片钳技术进行研究时，许多离子转运体和通道似乎受ATP依赖机制的调控。蛋白激酶显然是介导ATP效应的候选者，但其他机制也有涉及。这些机制包括生成磷脂酰肌醇磷酸作为第二信使的脂质激酶、ATP结合的变构效应、肌动蛋白细胞骨架的变化以及ATP依赖的磷脂酶。磷脂酰肌醇-4,5-二磷酸（PIP2）是一种可能的膜限定信使，可激活心脏钠钙交换体、ATP敏感性钾通道及其他内向整流钾通道。因此，磷脂酶C、脂质磷酸酶和脂质激酶对PIP2的调控会将表面膜转运与磷脂酰肌醇信号传导联系起来。钠氢交换通过一种不依赖磷酸化的机制被ATP激活，而离子共转运体则由多种蛋白激酶机制激活。上皮细胞中的离子转运可能对由ATP依赖的细胞信号机制调控的细胞骨架变化特别敏感。
