The periodic axon membrane skeleton leads to Na nanodomains but does not impact action potentials.
The periodic axon membrane skeleton leads to Na nanodomains but does not impact action potentials.
复制标题
周期性轴突膜骨架导致 Na 纳米域，但不影响动作电位。
DOI：
10.1016/j.bpj.2022.08.027
复制
发表时间：
2022
影响因子：
3.4
通讯作者：
Lykotrafitis,George
中科院分区：
文献类型：
--
作者：
Chai,Zhaojie;Tzingounis,AnastasiosV;Lykotrafitis,George
最近的工作已经确定，轴突有一个周期性的骨架结构，包括方位角肌动蛋白环连接通过纵向spectrin四聚体丝。这种结构赋予轴突结构完整性和机械稳定性。此外，电压门控钠通道遵循活性血影蛋白排列的周期性，间隔约190 nm的片段。钠通道的这种周期性排列对动作电位的产生和传播的影响尚不清楚。为了解决这个问题，我们在圆柱形隔室中使用Hodgkin-Huxley形式主义模拟动作电位，但是我们没有使用膜中电压门控钠通道的均匀分布，而是应用实验确定的周期性排列。我们发现，电压门控钠通道的周期性分布不会显著影响动作电位的产生或传播，而是导致由高密度钠纳米结构域引起的大的局部钠动作电流。此外，我们的模拟表明，周期性钠通道条之间的距离可以控制轴突的兴奋性，这表明以前未被充分认识的机制来调节神经元放电特性。总之，这项工作为轴突中钠通道的周期性排列的作用提供了一个关键的新见解，为未来的实验研究提供了基础。
Recent work has established that axons have a periodic skeleton structure comprising of azimuthal actin rings connected via longitudinal spectrin tetramer filaments. This structure endows the axon with structural integrity and mechanical stability. Additionally, voltage-gated sodium channels follow the periodicity of the active-spectrin arrangement, spaced ∼190 nm segments apart. The impact of this periodic arrangement of sodium channels on the generation and propagation of action potentials is unknown. To address this question, we simulated an action potential using the Hodgkin-Huxley formalism in a cylindrical compartment, but instead of using a homogeneous distribution of voltage-gated sodium channels in the membrane, we applied the experimentally determined periodic arrangement. We found that the periodic distribution of voltage-gated sodium channels does not significantly affect the generation or propagation of action potentials but instead leads to large, localized sodium action currents caused by high-density sodium nanodomains. Additionally, our simulations show that the distance between periodic sodium channel strips could control axonal excitability, suggesting a previously underappreciated mechanism to regulate neuronal firing properties. Together, this work provides a critical new insight into the role of the periodic arrangement of sodium channels in axons, providing a foundation for future experimental studies.