KChIP1 MODULATION OF Kv4.3-MEDIATED A-TYPE K+ CURRENTS AND REPETITIVE FIRING IN HIPPOCAMPAL INTERNEURONS
KChIP1 MODULATION OF Kv4.3-MEDIATED A-TYPE K+ CURRENTS AND REPETITIVE FIRING IN HIPPOCAMPAL INTERNEURONS
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DOI：
10.1016/j.neuroscience.2010.11.051
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发表时间：
2011-03-10
期刊：
影响因子：
3.3
通讯作者：
Lacaille, J. -C.
中科院分区：
文献类型：
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作者：
Bourdeau, M. L.;Laplante, I.;Lacaille, J. -C.
神经元A型K+通道调节动作电位波形、后向传播和放电频率。在位于腔隙-分子/辐射连接层(Lm/RAD)的海马CA1区中间神经元中，Kv4.3介导A型K+电流，Kv通道相互作用蛋白(KChIP)家族的Kv4β亚基KChIP1在这些细胞中特异表达。然而，这个辅助亚基在A型K+电流和神经元间兴奋性中的作用在很大程度上仍不清楚。因此，我们首先研究了KChIP1和Kv4.3在人胚胎肾293(HEK293)细胞中的通道相互作用，确定KChIP1的共表达调控了Kv4.3 A型电流的生物物理特性(从失活中恢复得更快，激活曲线左移，上升时间更快，衰退更慢)，这种调节可以被KChIP1短干扰RNA(SiRNA)选择性地阻止。接下来，我们研究了siRNA下调KChIP1对脑片培养的Lm/RAD中间神经元A-型钾电流的影响。KChIP1下调后，A型K+电流从失活状态恢复较慢，但其他特性没有变化。此外，KChIP1水平下调不影响动作电位波形和放电，但在阈值上去极化时增加放电频率，表明KChIP1调节神经元间兴奋性。KChIP1下调的影响是细胞特异性的，因为不表达KChIP1的CA1锥体细胞不受影响。总体而言，我们的发现表明，KChIP1与Kv4.3在Lm/RAD中间神经元中相互作用，使A-型电流更快地从失活中恢复，从而促进在持续活动中对放电的更强的抑制控制。(C)2011年IBRO。爱思唯尔有限公司出版。保留所有权利。
Neuronal A-type K+ channels regulate action potential waveform, back-propagation and firing frequency. In hippocampal CA1 interneurons located at the stratum lacunosum-moleculare/radiatum junction (LM/RAD), Kv4.3 mediates A-type K+ currents and a Kv4 beta-subunit of the Kv channel interacting protein (KChIP) family, KChIP1, appears specifically expressed in these cells. However, the functional role of this accessory subunit in A-type K+ currents and interneuron excitability remains largely unknown. Thus, first we studied KChIP1 and Kv4.3 channel interactions in human embryonic kidney 293 (HEK293) cells and determined that KChIP1 coexpression modulated the biophysical properties of Kv4.3 A-type currents (faster recovery from inactivation, leftward shift of activation curve, faster rise time and slower decay) and this modulation was selectively prevented by KChIP1 short interfering RNA (siRNA) knockdown. Next, we evaluated the effects of KChIP1 down-regulation by siRNA on A-type K+ currents in LM/RAD interneurons in slice cultures. Recovery from inactivation of A-type K+ currents was slower after KChIP1 down-regulation but other properties were unchanged. In addition, down-regulation of KChIP1 levels did not affect action potential waveform and firing, but increased firing frequency during suprathreshold depolarizations, indicating that KChIP1 regulates interneuron excitability. The effects of KChIP1 down-regulation were cell-specific since CA1 pyramidal cells that do not express KChIP1 were unaffected. Overall, our findings suggest that KChIP1 interacts with Kv4.3 in LM/RAD interneurons, enabling faster recovery from inactivation of A-type currents and thus promoting stronger inhibitory control of firing during sustained activity. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.