Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA.
Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA.
Curr Biol. 2023 May 8;33(9):1818-1824.e3. doi: 10.1016/j.cub.2023.03.043. Epub 2023 Apr 5.
The Na channels that are important for action potentials show rapid inactivation, a state in which they do not conduct, although the membrane potential remains depolarized. Rapid inactivation is a determinant of millisecond-scale phenomena, such as spike shape and refractory period. Na channels also inactivate orders of magnitude more slowly, and this slow inactivation has impacts on excitability over much longer timescales than those of a single spike or a single inter-spike interval. Here, we focus on the contribution of slow inactivation to the resilience of axonal excitability when ion channels are unevenly distributed along the axon. We study models in which the voltage-gated Na and K channels are unevenly distributed along axons with different variances, capturing the heterogeneity that biological axons display. In the absence of slow inactivation, many conductance distributions result in spontaneous tonic activity. Faithful axonal propagation is achieved with the introduction of Na channel slow inactivation. This "normalization" effect depends on relations between the kinetics of slow inactivation and the firing frequency. Consequently, neurons with characteristically different firing frequencies will need to implement different sets of channel properties to achieve resilience. The results of this study demonstrate the importance of the intrinsic biophysical properties of ion channels in normalizing axonal function.
对于动作电位很重要的 Na 通道表现出快速失活，在这种状态下它们不能传导，尽管膜电位仍然去极化。快速失活是毫秒级现象（如尖峰形状和不应期）的决定因素。Na 通道的失活速度也慢几个数量级，这种缓慢失活对兴奋性的影响时间尺度比单个尖峰或单个尖峰间隔长得多。在这里，我们关注的是当离子通道沿轴不均匀分布时，缓慢失活对轴突兴奋性弹性的贡献。我们研究了模型，其中电压门控 Na 和 K 通道沿具有不同方差的轴突不均匀分布，从而捕获了生物轴突表现出的异质性。在没有缓慢失活的情况下，许多电导分布导致自发紧张活动。通过引入 Na 通道缓慢失活，可以实现忠实的轴突传播。这种“归一化”效应取决于缓慢失活的动力学和放电频率之间的关系。因此，具有特征性不同放电频率的神经元将需要实现不同的通道特性集来实现弹性。本研究的结果表明离子通道的固有生物物理特性在轴突功能正常化中的重要性。
