Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons
Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons
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DOI：
10.1038/nn1019
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发表时间：
2003-03-01
影响因子：
25
通讯作者：
Surmeier, DJ
中科院分区：
文献类型：
--
作者：
Baranauskas, G;Tkatch, T;Surmeier, DJ
具有高频率放电能力的神经元--“快峰”(FS)神经元--是中枢运动和感觉回路的关键参与者。人们普遍认为，具有Kv3.1或Kv3.2亚基的K+通道是赋予神经元这种FS能力的快速、延迟整流(DR)电流的基础。然而，这些亚基在异源系统中的表达产生了比天然Kv3家族通道更具去极化电位的通道，这表明它们是不同的。一种可能性是，本地通道合并了一个修改门控的子单元。分子、电生理和药理学研究表明，Kv3.4亚基的一个剪接变体与大鼠脑FS神经元中的Kv3.1亚基共同组装。共组装提高了通道的尖峰再极化效率，从而缩短了尖峰持续时间并实现了更高的重复尖峰频率。这些结果表明，操纵K3.4亚单位的表达可能是控制FS神经元动态范围的有效手段。
Neurons with the capacity to discharge at high rates-'fast-spiking' (FS) neurons-are critical participants in central motor and sensory circuits. It is widely accepted that K+ channels with Kv3.1 or Kv3.2 subunits underlie fast, delayed-rectifier (DR) currents that endow neurons with this FS ability. Expression of these subunits in heterologous systems, however, yields channels that open at more depolarized potentials than do native Kv3 family channels, suggesting that they differ. One possibility is that native channels incorporate a subunit that modifies gating. Molecular, electrophysiological and pharmacological studies reported here suggest that a splice variant of the Kv3.4 subunit coassembles with Kv3.1 subunits in rat brain FS neurons. Coassembly enhances the spike repolarizing efficiency of the channels, thereby reducing spike duration and enabling higher repetitive spike rates. These results suggest that manipulation of K3.4 subunit expression could be a useful means of controlling the dynamic range of FS neurons.