Specific functions of synaptically localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse
Specific functions of synaptically localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse
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DOI：
10.1523/jneurosci.0722-05.2005
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发表时间：
2005-05-25
影响因子：
5.3
通讯作者：
Rudy, B
中科院分区：
文献类型：
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作者：
Goldberg, EM;Watanabe, S;Rudy, B
Kv 3亚家族的钾（K+）通道亚基（Kv3.1-Kv3.4）与其他电压门控K+通道相比显示出正移的激活电压依赖性和快速激活/失活动力学，这些特征赋予Kv 3通道有效且特异性地加速动作电位（AP）的复极化的能力。在皮质中，Kv3.1和Kv3.2蛋白在称为快速尖峰（FS）细胞的GABA能中间神经元亚群中显著表达，实际上是快速尖峰放电模式的重要决定因素。然而，除了在FS细胞胞体的表达，Kv3.1和Kv3.2蛋白也在FS细胞末端显著表达，表明Kv 3通道在神经递质释放中的作用。我们研究了1.0 mM的四乙基铵（TEA;其阻断Kv 3通道）对记录在II/III层新皮质锥体细胞中的抑制性突触电流的影响。1.0 mM TEA可使FS细胞的GABA释放增加近两倍，并降低配对脉冲比（PPR），低浓度TEA也可阻断非Kv 3亚家族K+通道，从而产生不可复制的效应。此外，在Kv3.1/Kv3.2双基因敲除（DKO）小鼠中，TEA的大作用不存在，尖峰诱发的GABA释放更大，PPR低于野生型小鼠。总之，这些结果表明，FS细胞终端的Kv 3通道的特定作用是不同的Kv 1和大电导Ca 2+激活的K+通道（也存在于FS细胞突触）。我们建议，在FS细胞终端突触本地化Kv 3通道保持AP简短，限制Ca 2+内流，因此释放概率，从而影响突触抑郁症的突触设计为持续的高频突触传递。
Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 channels the ability to accelerate the repolarization of the action potential (AP) efficiently and specifically. In the cortex, the Kv3.1 and Kv3.2 proteins are expressed prominently in a subset of GABAergic interneurons known as fast-spiking (FS) cells and in fact are a significant determinant of the fast-spiking discharge pattern. However, in addition to expression at FS cell somata, Kv3.1 and Kv3.2 proteins also are expressed prominently at FS cell terminals, suggesting roles for Kv3 channels in neurotransmitter release. We investigated the effect of 1.0 mM tetraethylammonium (TEA; which blocks Kv3 channels) on inhibitory synaptic currents recorded in layer II/III neocortical pyramidal cells. Spike-evoked GABA release by FS cells was enhanced nearly twofold by 1.0 mM TEA, with a decrease in the paired pulse ratio (PPR), effects not reproduced by blockade of the non-Kv3 subfamily K+ channels also blocked by low concentrations of TEA. Moreover, in Kv3.1/Kv3.2 double knock-out (DKO) mice, the large effects of TEA were absent, spike-evoked GABA release was larger, and the PPR was lower than in wild-type mice. Together, these results suggest specific roles for Kv3 channels at FS cell terminals that are distinct from those of Kv1 and large-conductance Ca2+-activated K+ channels (also present at the FS cell synapse). We propose that at FS cell terminals synaptically localized Kv3 channels keep APs brief, limiting Ca2+ influx and hence release probability, thereby influencing synaptic depression at a synapse designed for sustained high-frequency synaptic transmission.