Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
复制标题
DOI：
10.1523/jneurosci.3535-15.2016
复制
发表时间：
2016-01-27
影响因子：
5.3
通讯作者：
Hille, Bertil
中科院分区：
文献类型：
--
作者：
Kruse, Martin;Vivas, Oscar;Hille, Bertil
在神经元中，质膜磷脂酰肌醇4，5-二磷酸[PI（4，5）P-2]的损失导致胞吐减少和电兴奋性变化。因此，磷脂酶C激活后PI（4，5）P-2水平的恢复对于恢复基础神经元活性至关重要。然而，磷酸肌醇代谢的动力学尚未在神经元中分析。我们用电生理和光学方法测定了成年雄性Sprague-Dawley大鼠交感神经元中PI（4，5）P-2、4-磷酸磷脂酰肌醇、甘油二酯、1，4，5-三磷酸肌醇和Ca ~（2+）在毒蕈碱刺激后的动态变化。我们利用这一动力学信息来开发神经元磷脂酰肌醇代谢的定量描述。测量和分析显示并解释了交感神经元中PI（4，5）P-2的合成速度比电不可兴奋的tsA 201细胞中更快。它们可用于了解受体介导的磷脂酶C激活对神经元兴奋性和其他PI（4，5）P-2依赖性过程的动态影响。
In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P-2 levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P-2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+ upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P-2 in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P-2-dependent processes in neurons.