Kamiya Haruyuki
Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Front Neural Circuits. 2025 Jan 8;18:1505204. doi: 10.3389/fncir.2024.1505204. eCollection 2024.
A strong repetitive stimulus can occasionally enhance axonal excitability, leading to the generation of afterdischarge. This afterdischarge outlasts the stimulus period and originates either from the physiological spike initiation site, typically the axon initial segment, or from ectopic sites for spike generation. One of the possible mechanisms underlying the stimulus-induced ectopic afterdischarge is the local depolarization due to accumulated potassium ions surrounding the axonal membranes of the distal portion. In this study, the mechanisms were explored by computational approaches using a simple model of hippocampal mossy fibers implemented with the structure of axons and experimentally obtained properties of ionic conductances. When slight depolarization of distal axons was given in conjunction with the high-frequency stimulus, robust afterdischarges were triggered after cessation of the repetitive stimulus and lasted for a prolonged period after the stimulus. Each spike during the afterdischarge recorded from distal axons precedes that recorded from the soma, suggesting that the afterdischarge was ectopically generated from distal axons and propagated antidromically toward the soma. Notably, when potassium channels in the model are replaced with non-inactivating ones, repetitive stimuli fail to induce afterdischarge. These results suggested that the inactivating property of axonal potassium channels plays a crucial role in generating the afterdischarge. Accumulated inactivation of potassium channels during strong repetitive stimulation may alter mossy fiber excitability, leading to ectopic afterdischarges from sites distinct from the physiological spike initiation region.
强重复刺激偶尔会增强轴突兴奋性，导致发放后电位的产生。这种发放后电位持续时间超过刺激期，其起源于生理动作电位起始部位，通常是轴突起始段，或者是动作电位产生的异位部位。刺激诱导的异位发放后电位的一种可能机制是由于远端轴突膜周围钾离子积累导致的局部去极化。在本研究中，通过计算方法进行探索，使用具有轴突结构并通过实验获得离子电导特性的海马苔藓纤维简单模型。当在高频刺激的同时给予远端轴突轻微去极化时，在重复刺激停止后会触发强烈的发放后电位，并在刺激后持续较长时间。从远端轴突记录到的发放后电位期间的每个动作电位都先于从胞体记录到的动作电位，这表明发放后电位是从远端轴突异位产生并向胞体逆向传播的。值得注意的是，当模型中的钾通道被替换为非失活通道时，重复刺激无法诱导发放后电位。这些结果表明，轴突钾通道的失活特性在产生发放后电位中起关键作用。在强重复刺激期间钾通道的累积失活可能会改变苔藓纤维的兴奋性，导致从与生理动作电位起始区域不同的部位产生异位发放后电位。
