Block of hippocampal CAN channels by flufenamate
Block of hippocampal CAN channels by flufenamate
复制标题
DOI：
10.1016/s0006-8993(00)02275-7
复制
发表时间：
2000-06-09
期刊：
影响因子：
2.9
通讯作者：
Valenzuela, CF
中科院分区：
文献类型：
--
作者：
Partridge, LD;Valenzuela, CF
Ca 2+激活的非选择性阳离子（CAN）通道被胞质Ca 2+激活，I-CAN是神经元中许多缓慢去极化过程的基础，包括在兴奋性毒性中的假定作用。许多非神经元细胞中的CAN通道被非甾体类药物阻断，这些药物是二苯胺-2-羧酸酯（DPC）的衍生物。DPC衍生物氟芬那酯（FFA）对某些神经元具有复杂的作用，从而阻断CAN通道并增加[Ca 2 +]（i）。我们在这里报告，FFA，而不是母体化合物DPC，阻断海马CA 1神经元中的CAN通道。与其他神经元的情况一样，FFA的影响是复杂的，包括[Ca 2 +]（i）的持续上升。此外，CAN通道阻断能力的FFA持续存在，即使通道已被增强的钙离子依赖性过程。CAN通道阻断药物的使用对于通过Ca描绘CAN通道依赖性过程是重要的，并且可以为缺血中CAN通道依赖性事件的治疗提供基础。(C)2000 Elsevier Science B. V.保留所有权利。
Ca2+-activated non-selective cation (CAN) channels are activated by cytoplasmic Ca2+ and I-CAN underlies many slow depolarizing processes in neurons including a putative role in excitotoxicity. CAN channels in many non-neuronal cells are blocked by non-steroidal antiinflammatory drugs that are derivatives of diphenylamine-2-carboxylate (DPC). The DPC derivative flufenamate (FFA) has a complex effect on certain neurons, whereby it blocks CAN channels and increases [Ca2+](i). We report here that FFA, but not the parent compound, DPC, blocks CAN channels in hippocampal CAl neurons. As was the case in other neurons, the effects of FFA are complex and include a maintained rise in [Ca2+](i). Furthermore, the CAN channel blocking ability of FFA persists even when the channels have been potentiated by a Ca2+-dependent process. The use of a CAN channel-blocking drug is important for delineating CAN channel-dependent processes by a Ca and may provide a basis for therapy for CAN channel-dependent events in ischemia. (C) 2000 Elsevier Science B.V. All rights reserved.