Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons
Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons
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DOI：
10.1152/jn.1999.82.5.2476
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发表时间：
1999-11-01
影响因子：
2.5
通讯作者：
Leonard, CS
中科院分区：
文献类型：
--
作者：
Erisir, A;Lau, D;Leonard, CS
特异性K+通道在快速发放的新皮层中间神经元持续高频放电中的功能。神经生理学杂志。82：2476-2489，1999年。新皮层和海马的快速尖峰GABA能中间神经元发出高频的短暂动作电位，几乎没有尖峰频率适应。这些惊人的特性是如何产生的尚不清楚，尽管最近的证据表明含有Kv3.1-Kv3.2蛋白的K+通道起着重要作用。我们使用药理学和建模方法研究了这些通道在小鼠躯体感觉皮层的快速尖峰新皮层中间神经元的放电特性中的作用。低浓度的四乙基铵（TEA）（小于或等于1 mM），仅阻断少数已知的K+通道，包括Kv3.1-Kv3.2，严重损害动作电位复极和高频放电。稳定的去极化引起的尖峰列车的分析表明，虽然TEA的初始放电率的影响不大，它强烈地降低了放电频率后来的列车。这些作用似乎是特定于Kv3.1和Kv3.2通道，因为树枝毒素敏感的Kv 1通道和BK Ca 2+激活的K+通道，也具有高TEA敏感性，产生相反的效果或没有效果。电压钳实验证实了在快速尖峰神经元中存在Kv3.1-Kv3.2样电流，但在其他中间神经元中不存在。尖峰的形状变化的分析表明，Naf通道失活的放电速率减慢TEA产生的，计算机模拟支持的结论起着重要的作用。这些研究结果表明，Kv3.1-Kv3.2通道的独特性质，使持续的高频放电，促进恢复Na+通道失活，并通过最小化的持续时间后超极化的新皮层中间神经元。
Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J. Neurophysiol. 82: 2476-2489, 1999. Fast-spiking GABAergic interneurons of the neocortex and hippocampus fire high-frequency trains of brief action potentials with little spike-frequency adaptation. How these striking properties arise is unclear, although recent evidence suggests K+ channels containing Kv3.1-Kv3.2 proteins play an important role. We investigated the role of these channels in the firing properties of fast-spiking neocortical interneurons from mouse somatosensory cortex using a pharmacological and modeling approach. Low tetraethylammonium (TEA) concentrations (less than or equal to 1 mM), which block only a few known K+ channels including Kv3.1-Kv3.2, profoundly impaired action potential repolarization and high-frequency firing. Analysis of the spike trains evoked by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca2+-activated K+ channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3.2-like current in fast-spiking neurons, but not in other interneurons. Analysis of spike shape changes during the spike trains suggested that Naf channel inactivation plays a significant role in the firing-rate slowdown produced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enable sustained high-frequency firing by facilitating the recovery of Na+ channel inactivation and by minimizing the duration of the afterhyperpolarization in neocortical interneurons.