Differential modulation of Ih by 5-HT receptors in mouse CA1 hippocampal neurons
Differential modulation of Ih by 5-HT receptors in mouse CA1 hippocampal neurons
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DOI：
10.1046/j.1460-9568.2002.02072.x
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发表时间：
2002-07-01
影响因子：
3.4
通讯作者：
Richter, DW
中科院分区：
文献类型：
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作者：
Bickmeyer, U;Heine, M;Richter, DW
海马 CA1 锥体神经元表达各种类型的血清素 (5-HT) 受体，例如 5-HT1A、5-HT4 和 5-HT7 受体，它们与 Galpha(i) 或 Galpha(s) 蛋白偶联并作用于不同的细胞内信号通路。在本文中，我们验证了超极化激活电流 I-h 的这种差分血清素调节。 5-HT1A 受体的激活会导致电流诱导的超极化反应增强，而 5-HT4 受体激活后反应会下降。 5-HT1A受体激活后神经元静息电位超极化（-2.3+/-0.7mV），5-HT4受体激活使神经元去极化（+3.3+/-1.4mV）。毛喉素直接激活腺苷酸环化酶（AC）也会产生去极化。在电压钳中，I-h 电流通过其电压和时间依赖性特征以及 CsCl 或 ZD7288 的封锁来识别。 5-HT1A 受体的激活降低了 I-h 并将激活曲线在半最大激活时向负电压移动 -5 mV。 5-HT4 和 5-HT7 受体的激活增加了 I-h 并使激活曲线向右移动 +5 mV。 BIMU8 对 5-HT4 受体的特异性激活增加了膜电导，并且在一部分细胞中显示 I-h 增加，但没有引起激活曲线的显着变化。为了验证空间差异，我们选择性地将 BIMU8 应用到体细胞和树突上。仅体细胞应用诱导受体激活。这些数据通过抗 5-HT4A 受体抗体的免疫荧光染色得到证实，揭示了 CA1 区域体细胞的受体表达。针对 5-HT7 受体的新抗体也发现了类似的表达模式，该抗体揭示了锥体神经元细胞体上的免疫荧光染色。
CA1 pyramidal neurons of the hippocampus express various types of serotonin (5-HT) receptors, such as 5-HT1A, 5-HT4 and 5-HT7 receptors, which couple to Galpha(i) or Galpha(s) proteins and operate on different intracellular signalling pathways. In the present paper we verify such differential serotonergic modulation for the hyperpolarization-activated current I-h . Activation of 5-HT1A receptors induced an augmentation of current-induced hyperpolarization responses, while the responses declined after 5-HT4 receptors were activated. The resting potential of neurons hyperpolarized (-2.3 +/- 0.7 mV) after 5-HT1A receptor activation, activation of 5-HT4 receptors depolarized neurons (+3.3 +/- 1.4 mV). Direct activation of adenylyl cyclase (AC) by forskolin also produced a depolarization. In voltage clamp, the I-h current was identified by its characteristic voltage- and time-dependency and by blockade with CsCl or ZD7288. Activation of 5-HT1A receptors reduced I-h and shifted the activation curve to a more negative voltage by -5 mV at half-maximal activation. Activation of 5-HT4 and 5-HT7 receptors increased I-h and shifted the activation curve to the right by +5 mV. Specific activation of 5-HT4 receptors by BIMU8 increased membrane conductance and showed an increase in I-h in a subset of cells, but did not induce a significant alteration in the activation curve. In order to verify spatial differences, we applied BIMU8 selectively to the soma and to the dendrites. Only somatic application induced receptor activation. These data are confirmed by immunofluorescence stainings with an antibody against the 5-HT4A receptor, revealing receptor expression at the somata of the CA1 region. A similar expression pattern was found with a new antibody against 5-HT7 receptors which reveals immunofluorescence staining on the cell bodies of pyramidal neurons.