Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Departments of Pediatrics and Physiology and Biophysics, University of California, Irvine, Irvine, United States.
Elife. 2023 Feb 16;12:e81463. doi: 10.7554/eLife.81463.
Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of Na1.2 and Na1.6 channels lead to distinct contributions to AP initiation and propagation. While Na1.6 at the distal AIS promotes AP initiation and forward propagation, Na1.2 at the proximal AIS promotes the backpropagation of APs to the soma. Here, we show the small ubiquitin-like modifier (SUMO) pathway modulates Na channels at the AIS to increase neuronal gain and the speed of backpropagation. Since SUMO does not affect Na1.6, these effects were attributed to SUMOylation of Na1.2. Moreover, SUMO effects were absent in a mouse engineered to express Na1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of Na1.2 exclusively controls I generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.
电压门控钠离子通道位于轴突起始段（AIS），触发动作电位（AP），在皮质锥体神经元的兴奋性中发挥关键作用。Na1.2 和 Na1.6 通道的差异电生理特性和分布导致它们对 AP 起始和传播的贡献不同。虽然远端 AIS 上的 Na1.6 促进 AP 的起始和正向传播，但近端 AIS 上的 Na1.2 促进 AP 逆行传播到胞体。在这里，我们发现小泛素样修饰物（SUMO）途径调节 AIS 上的 Na 通道，以增加神经元增益和逆行传播的速度。由于 SUMO 不影响 Na1.6，这些效应归因于 Na1.2 的 SUMO 化。此外，在表达缺乏 SUMO 连接位点的 Na1.2-Lys38Gln 通道的工程化小鼠中，SUMO 效应缺失。因此，Na1.2 的 SUMO 化专门控制 I 生成和 AP 逆行传播，从而在突触整合和可塑性中发挥重要作用。
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