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首页> 外文期刊>American Journal of Physiology >IL-1beta directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current.
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IL-1beta directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current.

机译：IL-1beta通过渗透调节阳离子电流的上调直接激发离体大鼠视上神经元。

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Previous studies have shown that IL-1beta can excite the magnocellular neurosecretory cells (MNCs) of the hypothalamus. However, it is not known whether IL-1beta 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-1beta influences electrical activity in these cells. Here, we used patch-clamp recordings to examine the effects of IL-1beta on acutely isolated rat MNCs. We found that IL-1beta 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-1beta 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-1beta were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover, the effects of IL-1beta were mimicked and occluded by PGE2, and were inhibited by AH-23848, an antagonist of the PGE2 type 4 (i.e., EP4) receptor. The current evoked by IL-1beta was also abolished by 100 microM gadolinium (Gd3+), but was significantly larger when examined in cells preshrunk by negative pressure applied via the recording pipette. IL-1beta alone did not cause changes in cell volume nor in the mechanosensitivity of MNCs. We conclude that IL-1beta directly excites MNCs via an IL-1R1-mediated induction of PGE2 synthesis and EP4 receptor-dependent autocrine upregulation of the nonselective cation conductance that underlies osmoreception.
机译：先前的研究表明，IL-1β可以激发下丘脑的大细胞神经分泌细胞（MNC）。但是，尚不清楚IL-1β是否可以对MNC具有直接的IL-1受体1型（IL-1R1）介导的作用，而关于IL-1β影响这些细胞电活动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-1beta对急性分离的大鼠MNC的影响。我们发现IL-1beta以剂量依赖性方式直接激发MNC，并且该反应可以被IL-1R1的抑制剂阻断。 IL-1beta诱发的电流的钳位电压分析显示，电流-电压之间的线性关系介于-90和-20 mV之间，反向电位接近-35 mV。该值不受降低外部溶液中氯离子浓度的影响，表明参与了非选择性阳离子电导。 IL-1β的作用被环氧合酶抑制剂水杨酸钠抑制。而且，IL-1β的作用被PGE2模拟和封闭，并被AH-23848（PGE2 4型（即，EP4）受体的拮抗剂）抑制。 IL-1β诱发的电流也被100 microM ado（Gd3 +）取消，但在通过记录移液管施加负压预收缩的细胞中检查时，电流明显更大。单独的IL-1β不会引起细胞体积的改变，也不会引起MNC的机械敏感性的改变。我们得出结论，IL-1beta通过IL-1R1介导的PGE2合成和EP4受体依赖性自分泌上调非渗透性电导的非选择性阳离子电导直接激发MNC。

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