Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, United Kingdom.
Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-University, Munich, Germany.
Elife. 2022 May 5;11:e75219. doi: 10.7554/eLife.75219.
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.
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。在四个 Kv3 基因家族成员中，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 前突触末梢的亚基特异性作用。Kv3.3（而非 Kv3.1）的缺失减少了突触前 Kv3 通道免疫标记，增加了突触前 AP 持续时间，并促进了兴奋性递质释放；这反过来又增强了高频传递期间的短时间抑制。Kv3.3KO 对声音的反应延迟，自发性放电增加，而诱发放电减少，从而降低了信噪比。计算模型表明，Kv3.3KO 中的 EPSC 和短时间抑制增强反映了囊泡释放概率的增加和活动依赖性囊泡补充的加速。我们得出结论，Kv3.3 介导了快速复极化，用于短暂而精确的 AP，在这个谷氨酸能兴奋性突触处保持持续高频活动期间的传递。
