TREK-1 and TRAAK Are Principal K+ Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves
TREK-1 and TRAAK Are Principal K+ Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves
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DOI：
10.1016/j.neuron.2019.08.042
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发表时间：
2019-12-04
期刊：
影响因子：
16.2
通讯作者：
Gu, Jianguo G.
中科院分区：
文献类型：
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作者：
Kanda, Hirosato;Ling, Jennifer;Gu, Jianguo G.
神经冲动的快速传导在生命中是至关重要的，并且依赖于动作电位（AP）沿着有髓鞘神经沿着跨越朗维尔结（NR）。虽然NR是唯一的网站，AP可以在有髓鞘神经的神经传导过程中再生，离子通道机制的再生和传导的AP在哺乳动物的NR仍然不完全理解。在这里，我们表明，TREK-1和TRAAK，温度敏感和机械敏感的双孔域钾（K2 P）通道，聚集在大鼠三叉神经A β传入神经的NR的密度超过3,000倍，高于其胞体。这些K2 P通道，而不是在神经的其他部分中的电压门控K+通道，是在NR处快速AP复极化所必需的。此外，这些通道允许沿着有髓鞘传入神经的高速和高频AP传导，并且这些通道在NR处的功能丧失阻碍神经传导并损害动物的感觉行为反应。
Rapid conduction of nerve impulses is critical in life and relies on action potential (AP) leaps through the nodes of Ranvier (NRs) along myelinated nerves. While NRs are the only sites where APs can be regenerated during nerve conduction on myelinated nerves, ion channel mechanisms underlying the regeneration and conduction of APs at mammalian NRs remain incompletely understood. Here, we show that TREK-1 and TRAAK, the thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, are clustered at NRs of rat trigeminal A beta-afferent nerves with a density over 3,000-fold higher than that on their somas. These K2P channels, but not voltage-gated K+ channels as in other parts of nerves, are required for rapid AP repolarization at the NRs. Furthermore, these channels permit high-speed and high-frequency AP conduction along the myelinated afferent nerves, and loss of function of these channels at NRs retards nerve conduction and impairs sensory behavioral responses in animals.