Zheng Fumeng, Kamiya Haruyuki
Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Front Cell Neurosci. 2023 Apr 26;17:1154910. doi: 10.3389/fncel.2023.1154910. eCollection 2023.
Modification of axonal excitability directly impacts information transfer through the neuronal networks in the brain. However, the functional significance of modulation of axonal excitability by the preceding neuronal activity largely remains elusive. One remarkable exception is the activity-dependent broadening of action potential (AP) propagating along the hippocampal mossy fibers. The duration of AP is progressively prolonged during repetitive stimuli and facilitated presynaptic Ca entry and subsequent transmitter release. As an underlying mechanism, accumulated inactivation of axonal K channels during AP train has been postulated. As the inactivation of axonal K channels proceeds on a timescale of several tens of milliseconds slower than the millisecond scale of AP, the contribution of K channel inactivation in AP broadening needs to be tested and evaluated quantitatively. Using the computer simulation approach, this study aimed to explore the effects of the removal of the inactivation process of axonal K channels in the simple but sufficiently realistic model of hippocampal mossy fibers and found that the use-dependent AP broadening was completely abolished in the model replaced with non-inactivating K channels. The results demonstrated the critical roles of K channel inactivation in the activity-dependent regulation of axonal excitability during repetitive action potentials, which critically imparts additional mechanisms for robust use-dependent short-term plasticity characteristics for this particular synapse.
轴突兴奋性的改变直接影响大脑神经网络中的信息传递。然而，先前神经元活动对轴突兴奋性调节的功能意义在很大程度上仍不清楚。一个显著的例外是沿海马苔藓纤维传播的动作电位（AP）的活动依赖性展宽。在重复刺激期间，动作电位的持续时间逐渐延长，并促进突触前钙离子内流及随后的递质释放。作为一种潜在机制，有人推测在动作电位序列期间轴突钾通道的累积失活。由于轴突钾通道的失活在几十毫秒的时间尺度上进行，比动作电位的毫秒尺度要慢，因此需要对钾通道失活在动作电位展宽中的作用进行定量测试和评估。本研究采用计算机模拟方法，旨在探讨在简单但足够真实的海马苔藓纤维模型中去除轴突钾通道失活过程的影响，发现在用非失活钾通道替代的模型中，使用依赖性动作电位展宽完全消失。结果表明，钾通道失活在重复动作电位期间对轴突兴奋性的活动依赖性调节中起关键作用，这为该特定突触强大的使用依赖性短期可塑性特征赋予了额外的机制。
