Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis
Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis
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DOI：
10.1016/s0896-6273(02)00790-0
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发表时间：
2002-08-01
期刊：
影响因子：
16.2
通讯作者：
Hille, B
中科院分区：
文献类型：
--
作者：
Suh, BC;Hille, B
毒蕈碱受体对M电流通道的抑制增强了神经元的兴奋性。除了需要特定的G蛋白和参与一个身份不明的可扩散的第二信使外，对这种抑制的分子机制知之甚少。我们在这里证明，细胞内ATP是从毒蕈碱抑制中恢复KCNQ 2/KCNQ 3电流所必需的，其EC 50接近0.5 mM。用不可水解的ATP类似物替代ATP减缓或阻止恢复。ADP β S而非ADP也阻止了恢复。受体介导的抑制是不可逆的时，再循环的激动剂敏感池磷脂酰肌醇-4，5-二磷酸（PIP 2）被脂质激酶抑制剂阻断。从M电流的毒蕈碱调节中恢复需要PI 4-激酶的脂质磷酸化。
Suppression of M current channels by muscarinic receptors enhances neuronal excitability. Little is known about the molecular mechanism of this inhibition except the requirement for a specific G protein and the involvement of an unidentified diffusible second messenger. We demonstrate here that intracellular ATP is required for recovery of KCNQ2/KCNQ3 current from muscarinic suppression, with an EC50 of similar to0.5 mM. Substitution of nonhydrolyzable ATP analogs for ATP slowed or prevented recovery. ADPbetaS but not ADP also prevented the recovery. Receptor-mediated inhibition was irreversible when recycling of agonist-sensitive pools of phosphatidylinositol-4,5-bisphosphate (PIP2) was blocked by lipid kinase inhibitors. Lipid phosphorylation by PI4-kinase is required for recovery from muscarinic modulation of M current.