Zhu J J, Uhlrich D J
Department of Anatomy and Neuroscience Training Program, University of Wisconsin Medical School, Madison 53706, USA.
Neuroscience. 1998 Dec;87(4):767-81. doi: 10.1016/s0306-4522(98)00209-7.
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-beta-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 ml 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 ml 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 ml and m3 receptors were involved in the muscarinic depolarization was further supported by voltage-clamp analysis. This revealed that activation of the ml 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 IKleak and 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 IKleak and Ih. Given the fact that the ascending aminergic systems also depolarize geniculate relay cells via two receptors acting on IKleak and Ih, we concluded that ascending activating systems use common mechanisms to enact the depolarizing form of arousal in relay neurons.
我们在体外制备中使用全细胞记录技术，来研究毒蕈碱受体对大鼠外侧膝状核中继细胞的电生理作用。点滴施加毒蕈碱激动剂乙酰 -β-甲基胆碱会导致缓慢去极化，这种去极化持续数分钟。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。该反应对河豚毒素阻断突触传递也不敏感，表明是直接的毒蕈碱效应。毒蕈碱去极化由两个在时间上有所分离的成分组成。毒蕈碱反应的早期部分由大的内向电流介导，输入电阻变化很小，而后期部分由小的内向电流介导，同时输入电阻大幅增加。使用药理试剂来区分这两个成分。点滴施加毒蕈碱 m1 受体激动剂 McN - A - 343 只能模拟毒蕈碱反应的后期成分。低浓度哌仑西平能阻断后期成分这一结果支持了这一点。这些数据表明 m1 受体仅介导毒蕈碱反应的后期成分，而早期成分主要由 m3 受体介导。电压钳分析进一步支持了 m1 和 m3 受体都参与毒蕈碱去极化的观点。这表明 m1 受体的激活与内向钾电流 IKleak 的减少有关，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 的增加都有关。总之，我们的数据表明膝状中继细胞中的毒蕈碱反应是由两种受体的激活引起的，这两种受体调节 IKleak 和 Ih。鉴于上行胺能系统也通过作用于 IKleak 和 Ih 的两种受体使膝状中继细胞去极化这一事实，我们得出结论，上行激活系统利用共同机制在中继神经元中引发去极化形式的觉醒。
