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首页> 外文期刊>Journal of Neurophysiology >Histamine-induced excitatory responses in mouse ventromedial hypothalamic neurons: ionic mechanisms and estrogenic regulation.
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Histamine-induced excitatory responses in mouse ventromedial hypothalamic neurons: ionic mechanisms and estrogenic regulation.

机译：组胺诱导的小鼠腹膜下丘脑神经元的兴奋反应：离子机制和雌激素调节。

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摘要

Histamine is capable of modulating CNS arousal states by regulating neuronal excitability. In the current study, histamine action in the ventromedial hypothalamus (VMH), its related ionic mechanisms, and its possible facilitation by estrogen were investigated using whole cell patch-clamp recording in brain slices from ovariectomized female mice. Under current clamp, a bath application of histamine (20 microM) caused membrane depolarization, associated with an increased membrane resistance. In some cells, the depolarization was accompanied by action potentials. Histamine application also significantly reduced the latency of action potential evoked by current steps. Histamine-induced depolarization was not affected by either tetrodotoxin or Cd(2+). However, after blocking K(+) channels with tetraethylammonium, 4-aminopyridine, and Cs(+), depolarization was significantly decreased. Under voltage clamp, histamine-induced depolarization was associated with an inward current. The current-voltage relationshiprevealed that this inward current reversed near E(K). The histamine effect was mimicked by a histamine receptor 1 (H(1)) agonist, but not a histamine receptor 2 (H(2)) agonist. An H(1) antagonist, but not H(2) antagonist, abolished histamine responses. When ovariectomized mice were treated with estradiol benzoate (E2), histamine-induced depolarization was significantly enhanced with an increased percentage of cells showing action potential firing. These results suggest that histamine depolarized VMH neurons by attenuating a K(+) leakage current and this effect was mediated by H(1) receptor. E2 facilitated histamine-induced excitation of VMH neurons. This histamine effect may present a potential mechanism by which estrogens modulate the impact of generalized CNS arousal on a sexual arousal-related neuronal group.
机译：组胺能够通过调节神经元兴奋性来调节CNS觉醒状态。在当前的研究中，使用全细胞膜片钳记录在去卵巢雌性小鼠脑切片中，研究了组胺在腹侧下丘脑（VMH）中的作用，其相关离子机制以及雌激素可能的促进作用。在电流钳下，组胺（20 microM）的浴液施用会引起膜去极化，并伴有膜阻力增加。在某些细胞中，去极化伴随着动作电位。组胺的应用还显着减少了当前步骤引起的潜在动作潜伏期。组胺诱导的去极化不受河豚毒素或Cd（2+）的影响。但是，用四乙铵，4-氨基吡啶和Cs（+）阻断K（+）通道后，去极化作用明显降低。在电压钳制下，组胺引起​​的去极化与内向电流相关。电流-电压关系表明，该内向电流在E（K）附近反转。组胺效应是由组胺受体1（H（1））激动剂模拟的，而不是由组胺受体2（H（2））激动剂模拟的。一个H（1）拮抗剂，但不是H（2）拮抗剂，废除了组胺反应。当将去卵巢的小鼠用雌二醇苯甲酸酯（E2）处理时，组胺诱导的去极化作用显着增强，细胞中有显示动作电位的细胞百分比增加。这些结果表明，组胺通过减弱K（+）漏电流使VMH神经元去极化，并且这种作用是由H（1）受体介导的。 E2促进了组胺诱导的VMH神经元的兴奋。这种组胺作用可能提供了一种潜在的机制，雌激素可通过该机制调节广义CNS觉醒对与性觉醒相关的神经元群的影响。

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