M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region
M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region
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DOI：
10.1523/jneurosci.4463-06.2007
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发表时间：
2007-02-21
影响因子：
5.3
通讯作者：
Storm, Johan F.
中科院分区：
文献类型：
--
作者：
Hu, Hua;Vervaeke, Koen;Storm, Johan F.
为了了解皮层锥体神经元中的电信号处理是如何通过离子通道执行的，了解它们的亚细胞分布是至关重要的。M通道（由Kv7.2-Kv7.5/KCNQ 2-KCNQ 5基因编码）在神经元中具有多种重要功能，包括控制兴奋性、尖峰后电位、适应和θ共振。然而，这些通道的亚细胞分布仍然难以捉摸。为了确定M-通道在CA 1锥体神经元内的分布，我们在大鼠海马脑片中结合了从索马和顶端树突的全细胞膜片钳记录与局部药物应用。M通道开放剂（瑞替加滨[N-（2-氨基-4-（4-氟苄基氨基）-苯基）氨基甲酸乙酯]）和阻断剂（XE 991 [10，10-双（4-吡啶甲基）-9（10 H）-蒽酮]）均改变了体细胞阈下电压反应，但对局部树突反应无明显影响。在促进树突状细胞的Ca 2+尖峰的条件下，局部体细胞，但不是树突状细胞的应用M-通道阻滞剂（利诺吡啶和XE 991）增强了Ca 2+尖峰。同时树突和体细胞的全细胞记录表明，介质后超极化后，突发的尖峰经历了强烈的衰减沿着顶端树突和体细胞的XE 991应用程序完全阻止。最后，通过结合膜片钳和细胞外记录与计算机模拟，我们发现体周M通道减少了EPSP的总和。我们的结论是，功能M-通道似乎集中在CA 1锥体神经元的perisomatic区域，没有检测到M-通道活动的远端顶端树突。
To understand how electrical signal processing in cortical pyramidal neurons is executed by ion channels, it is essential to know their subcellular distribution. M-channels (encoded by Kv7.2-Kv7.5/KCNQ2-KCNQ5 genes) have multiple important functions in neurons, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Nevertheless, the subcellular distribution of these channels has remained elusive. To determine the M-channel distribution within CA1 pyramidal neurons, we combined whole-cell patch-clamp recording from the soma and apical dendrite with focal drug application, in rat hippocampal slices. Both a M-channel opener (retigabine [N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester]) and a blocker (XE991 [10,10-bis(4pyridinylmethyl)-9(10H)-antracenone]) changed the somatic subthreshold voltage response but had no observable effect on local dendritic responses. Under conditions promoting dendritic Ca2+ spikes, local somatic but not dendritic application of M-channel blockers (linopirdine and XE991) enhanced the Ca2+ spikes. Simultaneous dendritic and somatic whole-cell recordings showed that the medium afterhyperpolarization after a burst of spikes underwent strong attenuation along the apical dendrite and was fully blocked by somatic XE991 application. Finally, by combining patch- clamp and extracellular recordings with computer simulations, we found that perisomatic M-channels reduce the summation of EPSPs. We conclude that functional M-channels appear to be concentrated in the perisomatic region of CA1 pyramidal neurons, with no detectable M-channel activity in the distal apical dendrites.