Cell-type specific modulation of intrinsic firing properties and subthreshold membrane oscillations by the M(Kv7)-current in neurons of the entorhinal cortex.
Cell-type specific modulation of intrinsic firing properties and subthreshold membrane oscillations by the M(Kv7)-current in neurons of the entorhinal cortex.
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DOI：
10.1152/jn.00033.2007
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发表时间：
2007-11
影响因子：
2.5
通讯作者：
Motoharu Yoshida;A. Alonso
中科院分区：
文献类型：
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作者：
Motoharu Yoshida;A. Alonso
M 电流（通过 Kv7 通道的电流）是一种低阈值非失活钾电流，可被毒蕈碱激动剂抑制。最近的研究表明它在尖峰爆发产生和内在阈下θ共振中的作用，这两者对于记忆功能都很重要。然而，人们对其在内嗅皮层（EC）主细胞中的作用知之甚少。在这项研究中，我们在大鼠 EC 切片制备中使用全细胞贴片记录技术，研究了 M 电流阻滞剂利诺吡啶和 XE991 对 EC 主要细胞膜动力学的影响。当M电流被阻断时，II层非星状细胞（非SC）和III层细胞从强直放电切换到间歇放电模式，在此期间，II层非SC由于快速尖峰后除极（ADP）增加而表现出高频短时尖峰爆发。当以 50 Hz 的频率引发三个尖峰时，这两种类型的细胞会与缓慢的 ADP 发生反应，从而导致延迟放电。相比之下，II 层星状细胞 (SC) 和 V 层细胞从未表现出间歇性放电、爆发行为或延迟放电。在 M 电流阻断下，III 层和 V 层细胞的内在兴奋性显着增加，但 II 层 SC 和非 SC 没有显着增加。 M电流阻断对阈下兴奋性也有相反的影响，极大地抑制了V层细胞中的阈下膜电位振荡，但不抑制II层SC。因此，M 电流的调节以细胞类型依赖性方式改变 EC 主细胞的放电行为、内在兴奋性和阈下膜电位振荡。
The M-current (current through Kv7 channels) is a low-threshold noninactivating potassium current that is suppressed by muscarinic agonists. Recent studies have shown its role in spike burst generation and intrinsic subthreshold theta resonance, both of which are important for memory function. However, little is known about its role in principal cells of the entorhinal cortex (EC). In this study, using whole cell patch recording techniques in a rat EC slice preparation, we have examined the effects of the M-current blockers linopirdine and XE991 on the membrane dynamics of principal cells in the EC. When the M-current was blocked, layer II nonstellate cells (non-SCs) and layer III cells switched from tonic discharge to intermittent firing mode, during which layer II non-SCs showed high-frequency short-duration spike bursts due to increased fast spike afterdepolarization (ADP). When three spikes were elicited at 50 Hz, these two types of cells reacted with a slow ADP that drove delayed firing. In contrast, layer II stellate cells (SCs) and layer V cells never displayed intermittent firing, bursting behavior, or delayed firing. Under the M-current block, intrinsic excitability increased significantly in layer III and layer V cells but not in layer II SCs and non-SCs. The M-current block also had contrasting effects on the subthreshold excitability, greatly suppressing the subthreshold membrane potential oscillations in layer V cells but not in layer II SCs. Modulation of the M-current thus shifts the firing behavior, intrinsic excitability, and subthreshold membrane potential oscillations of EC principal cells in a cell-type-dependent manner.