Serotonin inhibits neuronal excitability by activating two-pore domain K+ channels in the entorhinal cortex
Serotonin inhibits neuronal excitability by activating two-pore domain K+ channels in the entorhinal cortex
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DOI：
10.1124/mol.107.034389
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Lei, Saobo
中科院分区：
文献类型：
--
作者：
Deng, Pan-Yue;Poudel, Kanta S.;Lei, Saobo
内嗅皮层（EC）被视为通往海马体的门户； EC 的浅层（I-III 层）将皮质输入投射传递至海马体，而 EC 的深层将海马输出投射传递回 EC 的浅层或其他皮质区域。 EC 的表层接收来自中缝核的强血清素能投射。然而，血清素在 EC 中的功能仍不清楚。在本研究中，我们研究了血清素介导的 EC 浅层（第二层和第三层）神经元兴奋性抑制的分子和细胞机制。血清素的应用通过激活双孔域 K+ 通道的 TWIK-1 型抑制 EC 浅层星状和锥体神经元的兴奋性。 5-HT 的作用是通过 5-HT1A 受体介导的，并且需要 G α(i3) 亚基和蛋白激酶 A 的功能。血清素介导的 EC 活性抑制导致海马功能的抑制。我们的研究提供了一种细胞机制，至少可以部分解释血清素在许多生理功能和神经系统疾病中的作用。
The entorhinal cortex (EC) is regarded as the gateway to the hippocampus; the superficial layers (layers I-III) of the EC convey the cortical input projections to the hippocampus, whereas deep layers of the EC relay hippocampal output projections back to the superficial layers of the EC or to other cortical regions. The superficial layers of the EC receive strong serotonergic projections from the raphe nuclei. However, the function of serotonin in the EC is still elusive. In the present study, we examined the molecular and cellular mechanisms underlying serotonin-mediated inhibition of the neuronal excitability in the superficial layers (layers II and III) of the EC. Application of serotonin inhibited the excitability of stellate and pyramidal neurons in the superficial layers of the EC by activating the TWIK-1 type of the two-pore domain K+ channels. The effects of 5-HT were mediated via 5-HT1A receptors and required the function of G alpha(i3) subunit and protein kinase A. Serotonin-mediated inhibition of EC activity resulted in an inhibition of hippocampal function. Our study provides a cellular mechanism that might at least partially explain the roles of serotonin in many physiological functions and neurological diseases.