Hilgemann D W, Ball R
Department of Physiology, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75235-9040, USA.
Science. 1996 Aug 16;273(5277):956-9. doi: 10.1126/science.273.5277.956.
Cardiac Na+,Ca2+ exchange is activated by a mechanism that requires hydrolysis of adenosine triphosphate (ATP) but is not mediated by protein kinases. In giant cardiac membrane patches, ATP acted to generate phosphatidylinositol-4,5-bisphosphate (PIP2) from phosphatidylinositol (PI). The action of ATP was abolished by a PI-specific phospholipase C (PLC) and recovered after addition of exogenous PI; it was reversed by a PIP2-specific PLC; and it was mimicked by exogenous PIP2. High concentrations of free Ca2+ (5 to 20 microM) accelerated reversal of the ATP effect, and PLC activity in myocyte membranes was activated with a similar Ca2+ dependence. Aluminum reversed the ATP effect by binding with high affinity to PIP2. ATP-inhibited potassium channels (KATP) were also sensitive to PIP2, whereas Na+,K+ pumps and Na+ channels were not. Thus, PIP2 may be an important regulator of both ion transporters and channels.
心脏钠钙交换由一种需要三磷酸腺苷（ATP）水解但不由蛋白激酶介导的机制激活。在巨大心脏膜片上，ATP作用于由磷脂酰肌醇（PI）生成磷脂酰肌醇-4,5-二磷酸（PIP2）。ATP的作用被PI特异性磷脂酶C（PLC）消除，并在添加外源性PI后恢复；它被PIP2特异性PLC逆转；并且它被外源性PIP2模拟。高浓度的游离钙离子（5至20微摩尔）加速了ATP效应的逆转，并且心肌细胞膜中的PLC活性以类似的钙离子依赖性被激活。铝通过与PIP2高亲和力结合来逆转ATP效应。ATP抑制的钾通道（KATP）也对PIP2敏感，而钠钾泵和钠通道则不敏感。因此，PIP2可能是离子转运体和通道的重要调节因子。
