Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing responses in relay cells of the rat lateral geniculate nucleus.
Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing responses in relay cells of the rat lateral geniculate nucleus.
复制标题
大鼠外侧膝状核中继细胞中两种毒蕈碱受体介导的去极化反应的细胞机制。
DOI：
10.1016/s0306-4522(98)00209-7
复制
发表时间：
1998
期刊：
影响因子：
3.3
通讯作者：
Uhlrich,DJ
中科院分区：
文献类型：
--
作者：
Zhu,JJ;Uhlrich,DJ
我们在体外制备中使用全细胞记录技术来检查毒蕈碱受体对大鼠外侧膝状核中继细胞的电生理作用。滴用毒蕈碱激动剂乙酰-β-甲基胆碱导致缓慢去极化，持续几分钟。该反应对烟碱拮抗剂六甲铵不敏感，但被毒蕈碱拮抗剂阿托品阻断。该反应对河豚毒素对突触传递的阻断也不敏感，表明具有直接的毒蕈碱作用。毒蕈碱去极化由时间上有些分离的两个部分组成。毒蕈碱反应的早期部分是由输入电阻几乎没有变化的大内向电流介导的，而后期部分是由与输入电阻大幅增加相关的小内向电流介导的。使用药理学试剂来区分这两种成分。滴注 McN-A-343（一种 m1 受体激动剂）只能模拟毒蕈碱反应的后期部分。这得到了后一个组分被低浓度哌仑西平阻断的结果的支持。这些数据表明m1受体仅介导毒蕈碱反应的晚期成分，而早期成分主要由m3受体介导。 m1 和 m3 受体均参与毒蕈碱去极化的观点得到了电压钳分析的进一步支持。这表明m1受体的激活与内向钾电流IKleak的减少相关，而m3受体的激活可能与IKleak的减少和超极化激活的阳离子电流Ih的增加相关。总之，我们的数据表明膝状中继细胞中的毒蕈碱反应是由调节 IKleak 和 Ih 的两个受体的激活引起的。鉴于上行胺能系统还通过作用于 IKleak 和 Ih 的两个受体使膝状中继细胞去极化，我们得出结论，上行激活系统使用常见机制在中继神经元中产生去极化形式的唤醒。
We used the whole-cell recording technique in an in vitro preparation to examine the electrophysiological actions of the muscarinic receptors on relay cells in the rat lateral geniculate nucleus. Drop application of the muscarinic agonist acetyl-β-methylcholine resulted in a slow depolarization that persisted for several minutes. The response was insensitive to the nicotinic antagonist hexamethonium, but was blocked by atropine, a muscarinic antagonist. The response was also insensitive to blockade of synaptic transmission by tetrodotoxin, indicating a direct muscarinic effect. The muscarinic depolarization consisted of two components that were somewhat separated in time. The early portion of the muscarinic response was mediated by a large inward current with little change in input resistance, while the later portion was mediated by a small inward current associated with a large increase in input resistance. Pharmacological agents were used to distinguish the two components. Drop application of McN-A-343, an m1 receptor agonist, could only mimic the later component of the muscarinic response. This was supported by the result that the later component was blocked by low concentrations of pirenzepine. These data suggest that the m1 receptor only mediates the late component of the muscarinic response, while the early component is mainly mediated by the m3 receptor. The idea that both m1 and m3 receptors were involved in the muscarinic depolarization was further supported by voltage-clamp analysis. This revealed that activation of the m1 receptor was associated with a decrease in an inward potassium current, IKleak, while activation of the m3 receptor was likely associated with both a decrease in IKleakand an increase in the hyperpolarization-activated cation current Ih. In summary, our data suggest that muscarinic responses in geniculate relay cells result from the activation of two receptors, which modulate IKleakand Ih. Given the fact that the ascending aminergic systems also depolarize geniculate relay cells via two receptors acting on IKleakand Ih, we concluded that ascending activating systems use common mechanisms to enact the depolarizing form of arousal in relay neurons.