Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion
Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion
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DOI：
10.1113/jphysiol.2003.046250
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发表时间：
2003-07-01
影响因子：
5.5
通讯作者：
Forsythe, ID
中科院分区：
文献类型：
--
作者：
Dodson, PD;Billups, B;Forsythe, ID
电压门控K+通道激活接近静息膜电位广泛表达和差异定位于轴突，突触前末梢和细胞体。有大量的证据表明，Kv 1亚基在许多中央突触终端的本地化，但很少有线索，他们的突触前功能。本研究采用树状毒素-K（DTX-K）和巨噬细胞毒素-K α（TsTX-K α）分别阻断大鼠Held肾盏含Kv1.1和Kv1.2的通道，研究了突触前Kv 1通道在大鼠海马神经元突触中的作用。我们发现，Kv1.2同源体负责三分之二的突触前低阈值电流，而Kv1.1/Kv1.2异源体贡献剩余的电流。这些通道位于轴突和突触终末之间的过渡区，与位于突触终末本身的高阈值K+通道亚基Kv3.1形成对比。Kv 1同聚体不存在从浓密的细胞胞体（从花萼轴突出现），而不是体细胞低阈值通道由异聚体含有Kv1.1。Kv1.2和Kv1.6亚基。从花萼的电流钳记录表明，每个突触前动作电位（AP），其次是去极化后电位（DAP）持续约50 ms。Kv1.1/Kv1.2异聚体对终端兴奋性的影响不大，因为DTX-K没有改变AP发射。然而，TsTX-Ka增加了DAP幅度，使终端更接近用于产生额外AP的阈值。成对的前和突触后记录证实，这异常AP诱发兴奋性突触后电流（EPSC）。我们的结论是，Kv1.2通道有一个一般的突触前功能，抑制终端过度兴奋在去极化后电位。
Voltage-gated K+ channels activating close to resting membrane potentials are widely expressed and differentially located in axons, presynaptic terminals and cell bodies. There is extensive evidence for localisation of Kv1 subunits at many central synaptic terminals but few clues to their presynaptic function. We have used the calyx of Held to investigate the role of presynaptic Kv1 channels in the rat by selectively blocking Kv1.1 and Kv1.2 containing channels with dendrotoxin-K (DTX-K) and tityustoxin-Kalpha (TsTX-Kalpha) respectively. We show that Kv1.2 homomers are responsible for two-thirds of presynaptic low threshold current, whilst Kv1.1/Kv1.2 heteromers contribute the remaining current. These channels are located in the transition zone between the axon and synaptic terminal, contrasting with the high threshold K+ channel subunit Kv3.1 which is located on the synaptic terminal itself. Kv1 homomers were absent from bushy cell somata (from which the calyx axons arise); instead somatic low threshold channels consisted of heteromers containing Kv1.1. Kv1.2 and Kv1.6 subunits. Current-clamp recording from the calyx showed that each presynaptic action potential (AP) was followed by a depolarising after-potential (DAP) lasting around 50 ms. Kv1.1/Kv1.2 heteromers had little influence on terminal excitability, since DTX-K did not alter AP firing. However TsTX-Ka increased DAP amplitude, bringing the terminal closer to threshold for generating an additional AP. Paired pre- and postsynaptic recordings confirmed that this aberrant AP evoked an excitatory postsynaptic current (EPSC). We conclude that Kv1.2 channels have a general presynaptic function in suppressing terminal hyperexcitability during the depolarising after-potential.