Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
J Comput Neurosci. 2020 Nov;48(4):377-386. doi: 10.1007/s10827-020-00766-1. Epub 2020 Oct 15.
Channelopathies involving acquired or genetic modifications of the delayed rectifier K channel Kv1.1 include phenotypes characterized by enhanced neuronal excitability. Affected Kv1.1 channels exhibit combinations of altered expression, voltage sensitivity, and rates of activation and deactivation. Computational modeling and analysis can reveal the potential of particular channelopathies to alter neuronal excitability. A dynamical systems approach was taken to study the excitability and underlying dynamical structure of the Hodgkin-Huxley (HH) model of neural excitation as properties of the delayed rectifier K channel were altered. Bifurcation patterns of the HH model were determined as the amplitude of steady injection current was varied simultaneously with single parameters describing the delayed rectifier rates of activation and deactivation, maximal conductance, and voltage sensitivity. Relatively modest changes in the properties of the delayed rectifier K channel analogous to what is described for its channelopathies alter the bifurcation structure of the HH model and profoundly modify excitability of the HH model. Channelopathies associated with Kv1.1 can reduce the threshold for onset of neural activity. These studies also demonstrate how pathological delayed rectifier K channels could lead to the observation of the generalized Hopf bifurcation and, perhaps, other variants of the Hopf bifurcation. The observed bifurcation patterns collectively demonstrate that properties of the nominal delayed rectifier in the HH model appear optimized to permit activation of the HH model over the broadest possible range of input currents.
涉及延迟整流钾通道 Kv1.1 的获得性或遗传性改变的通道病包括以增强神经元兴奋性为特征的表型。受影响的 Kv1.1 通道表现出表达、电压敏感性以及激活和失活速率改变的组合。计算建模和分析可以揭示特定通道病改变神经元兴奋性的潜力。采用动力系统方法研究了神经兴奋的 Hodgkin-Huxley (HH) 模型的兴奋性和潜在动力学结构，因为延迟整流钾通道的特性发生了改变。当描述延迟整流激活和失活速率、最大电导和电压敏感性的单个参数与稳定注入电流的幅度同时变化时，确定了 HH 模型的分岔模式。类似于描述其通道病的情况，延迟整流钾通道特性的相对适度改变改变了 HH 模型的分岔结构，并深刻地改变了 HH 模型的兴奋性。与 Kv1.1 相关的通道病可以降低神经活动开始的阈值。这些研究还表明，病理性延迟整流钾通道如何导致广义 Hopf 分岔的观察，以及可能的 Hopf 分岔的其他变体。观察到的分岔模式共同表明，HH 模型中名义延迟整流的特性似乎经过优化，以允许 HH 模型在尽可能广泛的输入电流范围内激活。
