Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles.
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| Abstract |
Since their discovery decades ago, the primary physiological and pathological effects of potassium channels have been attributed to their ion conductance, which sets membrane potential and repolarizes action potentials. For example, Kv3 family channels regulate neurotransmitter release by repolarizing action potentials. Here we report a surprising but crucial function independent of potassium conductance: by organizing the F-actin cytoskeleton in mouse nerve terminals, the Kv3.3 protein facilitates slow endocytosis, rapid endocytosis, vesicle mobilization to the readily releasable pool, and recovery of synaptic depression during repetitive firing. A channel mutation that causes spinocerebellar ataxia inhibits endocytosis, vesicle mobilization, and synaptic transmission during repetitive firing by disrupting the ability of the channel to nucleate F-actin. These results unmask novel functions of potassium channels in endocytosis and vesicle mobilization crucial for sustaining synaptic transmission during repetitive firing. Potassium channel mutations that impair these "non-conducting" functions may thus contribute to generation of diverse neurological disorders.
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| Authors | Xin-Sheng Wu, Shobana Subramanian, Yalan Zhang, Bo Shi, Jessica Xia, Tiansheng Li, Xiaoli Guo, Lynda El-Hassar, Klara Szigeti-Buck, Jorge Henao-Mejia, Richard A Flavell, Tamas L Horvath, Elizabeth A Jonas, Leonard K Kaczmarek, Ling-Gang Wu |
| Journal | Neuron (Neuron) Vol. 109 Issue 6 Pg. 938-946.e5 (03 17 2021) ISSN: 1097-4199 [Electronic] United States |
| PMID | 33508244 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't) |
| Copyright | Published by Elsevier Inc. |
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