Département de Physiologie, Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada.
Neuroscience. 2011 Mar 10;176:173-87. doi: 10.1016/j.neuroscience.2010.11.051. Epub 2010 Dec 1.
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 β-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.
神经元 A 型钾 (K+) 通道调节动作电位波形、反向传播和放电频率。在位于腔隙 - 分子层/辐射层交界处 (LM/RAD) 的海马 CA1 中间神经元中，Kv4.3 介导 A 型 K(+) 电流，而 Kv 通道相互作用蛋白 (KChIP) 家族的 Kv4β 亚基，KChIP1，似乎特异性表达于这些细胞中。然而，这种辅助亚基在 A 型 K(+) 电流和中间神经元兴奋性中的功能作用在很大程度上仍然未知。因此，我们首先在人胚肾 293 (HEK293) 细胞中研究了 KChIP1 和 Kv4.3 通道的相互作用，并确定 KChIP1 共表达调节 Kv4.3 A 型电流的生物物理特性（失活后更快恢复、激活曲线左移、更快上升时间和更慢衰减），这种调节可通过 KChIP1 短发夹 RNA (siRNA) 敲低选择性预防。接下来，我们评估了 siRNA 下调 KChIP1 对切片培养中 LM/RAD 中间神经元 A 型 K(+) 电流的影响。失活后 A 型 K(+) 电流的恢复变慢，但其他特性不变。此外，下调 KChIP1 水平不会影响动作电位波形和放电，但会增加阈上去极化期间的放电频率，表明 KChIP1 调节中间神经元兴奋性。KChIP1 下调的影响是细胞特异性的，因为不表达 KChIP1 的 CA1 锥体神经元不受影响。总的来说，我们的发现表明 KChIP1 在 LM/RAD 中间神经元中与 Kv4.3 相互作用，使 A 型电流更快地恢复失活，从而在持续活动期间促进更强的抑制控制放电。
