IL-1β directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current
IL-1β directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current
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DOI：
10.1152/ajpregu.00716.2005
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发表时间：
2006-05-01
影响因子：
2.8
通讯作者：
Bourque, CW
中科院分区：
文献类型：
--
作者：
Chakfe, Y;Zhang, ZZ;Bourque, CW
先前的研究表明，IL-1 β可以兴奋下丘脑的大细胞神经分泌细胞（MNCs）。然而，目前尚不清楚IL-1 β是否可以对MNC具有直接的IL-1受体1型（IL-1 R1）介导的作用，并且对IL-1 β影响这些细胞中电活性的细胞机制知之甚少。在这里，我们使用膜片钳记录来检查IL-1 β对急性分离的大鼠MNCs的影响。我们发现IL-1 β以剂量依赖性方式直接兴奋MNC，并且这种反应可以被IL-1 R1的抑制剂阻断。对IL-1 β诱发的电流的电压钳分析揭示了在-90和-20 mV之间的线性电流-电压关系，以及接近-35 mV的反转电位。该值不受影响，通过减少氯离子的浓度在外部溶液中，表明参与的非选择性阳离子电导。IL-1 β的作用可被环氧化酶抑制剂水杨酸钠抑制。而且。IL-1 β的作用被PGE（2）模拟和封闭，并被AH-23848抑制，AH-23848是PGE（2）4型的拮抗剂（即，EP 4）受体。由IL-1 β诱发的电流也被100 μ M钆（Gd 3+）消除，但在通过记录移液管施加负压的预收缩细胞中检查时明显更大。单独的IL-1 β不会引起细胞体积的变化，也不会引起MNCs的机械敏感性的变化。我们的结论是，IL-1 β通过IL-1 R1介导的PGE（2）合成诱导和EP 4受体依赖的非选择性阳离子电导的自分泌上调直接兴奋MNC，而非选择性阳离子电导是突触接受的基础。
Previous studies have shown that IL-1 beta can excite the magnocellular neurosecretory cells (MNCs) of the hypothalamus. However, it is not known whether IL-1 beta can have direct IL-1 receptor type 1 (IL-1R1)-mediated effects on MNCs, and little is known about the cellular mechanisms by which IL-1 beta influences electrical activity in these cells. Here, we used patch-clamp recordings to examine the effects of IL-1 beta on acutely isolated rat MNCs. We found that IL-1 beta directly excites MNCs in a dose-dependent manner and that this response can be blocked by an inhibitor of the IL-1R1. Voltage-clamp analysis of the current evoked by IL-1 beta revealed a linear current-voltage relationship between -90 and -20 mV, and a reversal potential near -35 mV. This value was not affected by reducing the concentration of chloride ions in the external solution, indicating the involvement of a nonselective cation conductance. The effects of IL-1 beta were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover. the effects of IL-1 beta were mimicked and occluded by PGE(2), and were inhibited by AH-23848, an antagonist of the PGE(2) type 4 (i.e., EP4) receptor. The current evoked by IL-1 beta was also abolished by 100 mu M gadolinium (Gd3+), but was significantly larger when examined in cells preshrunk by negative pressure applied via the recording pipette. IL-1 beta alone did not cause changes in cell volume nor in the mechanosensitivity of MNCs. We conclude that IL-1 beta directly excites MNCs via an IL-1R1-mediated induction of PGE(2) synthesis and EP4 receptor-dependent autocrine upregulation of the nonselective cation conductance that underlies osmoreception.