NALCN channels enhance the intrinsic excitability of spinal projection neurons.
NALCN channels enhance the intrinsic excitability of spinal projection neurons.
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DOI：
10.1097/j.pain.0000000000001258
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发表时间：
2018-09
期刊：
影响因子：
7.4
通讯作者：
Baccei ML
中科院分区：
文献类型：
--
作者：
Ford NC;Ren D;Baccei ML
脊髓投射神经元将伤害性信号传递到包括臂旁核（PB）在内的多个脑区，这有助于疼痛感知的情绪效价。尽管投射神经元对疼痛处理的重要性很明显，但我们对形成其内在膜兴奋性的因素的理解仍然有限。在这里，我们调查的Na 1泄漏通道NALCN在调节活动的spino-PB神经元在发育中的啮齿动物的潜在作用。药理学减少NALCN电流（INALCN），或NALCN通道的基因缺失，显着降低了I层脊髓PB神经元的内在兴奋性。此外，P物质（SP）通过下游Src激酶信号传导激活上行投射神经元中的INALCN，NALCN的敲除阻止了该神经元群体中SP诱发的动作电位放电。这些结果确定，第一次，NALCN作为一个强大的调节中枢疼痛回路内的神经元活动，也阐明了一个额外的离子机制，SP可以调节脊髓伤害性处理。总的来说，这些研究结果表明，脊髓PB神经元内的NALCN电导水平紧密地控制着向大脑的上行伤害性传递，从而潜在地影响疼痛感知。
Spinal projection neurons convey nociceptive signals to multiple brain regions including the parabrachial (PB) nucleus, which contributes to the emotional valence of pain perception. Despite the clear importance of projection neurons to pain processing, our understanding of the factors that shape their intrinsic membrane excitability remains limited. Here, we investigate a potential role for the Na 1 leak channel NALCN in regulating the activity of spino-PB neurons in the developing rodent. Pharmacological reduction of NALCN current (INALCN), or the genetic deletion of NALCN channels, significantly reduced the intrinsic excitability of lamina I spino-PB neurons. In addition, substance P (SP) activated INALCN in ascending projection neurons through downstream Src kinase signaling, and the knockout of NALCN prevented SP-evoked action potential discharge in this neuronal population. These results identify, for the first time, NALCN as a strong regulator of neuronal activity within central pain circuits and also elucidate an additional ionic mechanism by which SP can modulate spinal nociceptive processing. Collectively, these findings indicate that the level of NALCN conductance within spino-PB neurons tightly governs ascending nociceptive transmission to the brain and thereby potentially influences pain perception.
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DOI：
10.1126/science.aac8653
发表时间：
2015-10-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bourane S;Duan B;Koch SC;Dalet A;Britz O;Garcia-Campmany L;Kim E;Cheng L;Ghosh A;Ma Q;Goulding M
通讯作者：
Goulding M
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
2.5
作者：
Dai, Yue;Jordan, Larry M.
通讯作者：
Jordan, Larry M.
影响因子：
2.5
作者：
Bruehl, C;Witte, OW
通讯作者：
Witte, OW
影响因子：
64.8
作者：
Cao, YQ;Mantyh, PW;Basbaum, AI
通讯作者：
Basbaum, AI