Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release
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DOI：
10.1113/jphysiol.2006.111336
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发表时间：
2006-10-01
影响因子：
5.5
通讯作者：
Storm, J. F.
中科院分区：
文献类型：
--
作者：
Vervaeke, K.;Gu, N.;Storm, J. F.
M电流（I-M）在调节神经元兴奋性中起关键作用。Kv 7/KCNQ亚基的突变，I-M的分子相关物，与家族性人类癫痫综合征相关。Kv 7/KCNQ亚基广泛表达，并且在几种类型的神经元胞体中记录了I-M，但M通道的亚细胞分布仍然不清楚。通过结合场电位，全细胞和细胞内的记录，从区域CA 1在大鼠海马切片，和计算建模，我们提供的证据功能M-通道在无髓鞘的轴突在大脑中。我们的数据表明，突触前M通道可以调节轴突兴奋性和突触传递，只要轴突被去极化到I-M激活范围（超过类似-65 mV）。在此，通过增加细胞外K+浓度（[K+]（0））实现这种去极化。在[K+]（0）（7-11 mM）中度升高的情况下的细胞外记录表明，特异性M通道阻滞剂XE 991以[K+]（0）依赖性方式降低了突触前纤维齐射和场EPSP的振幅，无论是在放射层还是在分子层中。M通道开放剂瑞替加宾则有相反的效果。[K+]（0）越高，XE 991和瑞替加滨的作用越大。类似的药理学调制的EPSPs;记录从CA 1锥体神经元细胞内，同时阻断突触后K+通道与细胞内Cs+，证实了活跃的M-通道位于突触前。轴突模型的计算分析表明，突触前I-M可以控制Na+通道失活，从而影响突触前动作电位的幅度和Ca 2+内流，提供轴突膜电位充分去极化。最后，我们比较了阻断I-M对海马CA 3区锥体神经元胞体和轴突锋电位后除极和爆发的影响。在标准[K+]（0）（2.5 mM）中，XE 991增加ADP并促进索马的爆发放电，但不在轴突中。然而，I-M有助于在轴突的不应期时，尖峰被扩大了低剂量的4-氨基吡啶（200 μ M）。我们的研究结果表明，功能Kv 7/KCNQ/M-通道存在于大脑中的无髓鞘轴突，这些通道可能有不同的兴奋性取决于它们的亚细胞定位的影响。
M-current (I-M) plays a key role in regulating neuronal excitability. Mutations in Kv7/KCNQ subunits, the molecular correlates of I-M, are associated with a familial human epilepsy syndrome. Kv7/KCNQ subunits are widely expressed, and I-M has been recorded in somata of several types of neurons, but the subcellular distribution of M-channels remains elusive. By combining field-potential, whole-cell and intracellular recordings from area CA1 in rat hippocampal slices, and computational modelling, we provide evidence for functional M-channels in unmyelinated axons in the brain. Our data indicate that presynaptic M-channels can regulate axonal excitability and synaptic transmission, provided the axons are depolarized into the I-M activation range (beyond similar to - 65 mV). Here, such depolarization was achieved by increasing the extracellular K+ concentration ([K+](0)). Extracellular recordings in the presence of moderately elevated [K+](0) (7-11 mM), showed that the specific M-channel blocker XE991 reduced the amplitude of the presynaptic fibre volley and the field EPSP in a [K+](0)-dependent manner, both in stratum radiatum and in stratum lacknosum moleculare. The M-channel opener, retigabine, had opposite effects. The higher the [K+](0), the greater the effects of XE991 and retigabine. Similar pharmacological modulation of EPSPs; recorded intracellularly from CA1 pyramidal neurons, while blocking postsynaptic K+ channels with intracellular Cs+, confirmed that active M-channels are located presynaptically. Computational analysis with an axon model showed that presynaptic I-M can control Na+ channel inactivation and thereby affect the presynaptic action potential amplitude and Ca2+ influx, provided the axonal membrane potential is sufficiently depolarized. Finally, we compared the effects of blocking I-M on the spike after-depolarization and bursting in CA3 pyramidal neuron somata versus their axons. In standard [K+](0) (2.5 mM), XE991 increased the ADP and promoted burst firing at the soma, but not in the axons. However, I-M contributed to the refractory period in the axons when spikes were broadened by a low dose 4-aminopyridine (200 mu M). Our results indicate that functional Kv7/KCNQ/M-channels are present in unmyelinated axons in the brain, and that these channels may have contrasting effects on excitability depending on their subcellular localization.