Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse.
Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse.
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DOI：
10.7554/elife.75219
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发表时间：
2022-05-05
期刊：
影响因子：
7.7
通讯作者：
Forsythe, Ian D.
中科院分区：
文献类型：
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作者：
Richardson, Amy;Ciampani, Victoria;Stancu, Mihai;Bondarenko, Kseniia;Newton, Sherylanne;Steinert, Joern R.;Pilati, Nadia;Graham, Bruce P.;Kopp-Scheinpflug, Conny;Forsythe, Ian D.
Kv3钾电流介导动作电位（AP）的快速复极化，支持快速尖峰和高重复率。Kv3基因家族的四个成员中，Kv3.1和Kv3.3在听觉脑干中高度表达，我们利用这一点来测试在小鼠的Held突触前末梢的萼中的亚单位特异性作用。缺失Kv3.3（而不是Kv3.1）减少突触前Kv3通道免疫标记，增加突触前AP持续时间和促进兴奋性递质释放，这反过来又增强了短期抑郁症在高频传输。在Kv3.3KO中，对声音的反应延迟，具有较高的自发放电和较低的诱发放电，从而降低信噪比。计算模型表明，增强EPSC和短期抑郁症的Kv3.3KO反映了囊泡释放概率增加和加速活性依赖性囊泡补充。我们的结论是，Kv3.3介导快速复极化短精确AP，保存传输过程中持续的高频率活动在这mammatergic兴奋性突触。
Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.