High-frequency stimulation of excitable cells and networks.
High-frequency stimulation of excitable cells and networks.
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DOI：
10.1371/journal.pone.0081402
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Weinberg SH
中科院分区：
文献类型：
--
作者：
Weinberg SH
高频（HF）刺激已被证明可以阻断包括神经元和心肌细胞在内的可兴奋细胞的传导。然而，传导阻滞的确切机制尚不清楚。使用多尺度方法，HF刺激的影响进行了研究，在简化的FitzhHugh-Nagumo和生物病理学详细的Hodgkin-Huxley模型。在这两种模型中，HF刺激改变了响应于恒定施加电流的重复放电的幅度和频率，并增加了响应于短暂施加电流脉冲的诱发单个动作电位的阈值。此外，可兴奋细胞不能唤起单个动作电位或在HF刺激幅度的临界值以上重复放电。在FitzHugh-Nagumo模型中确定了临界值和阈值的解析表达式。在Hodgkin-Huxley模型中，HF刺激改变了离子电流门控的动力学，改变了稳态激活、失活和时间常数曲线，提示了传导阻滞的几种可能机制。最后，我们表明，HF刺激的神经元网络的电活动放电率降低，增加网络同步，并为一个足够大的HF刺激，导致完全电静止。在这项研究中，我们展示了一种新的方法来研究HF刺激的生物药理学详细的离子模型的可兴奋细胞，证明可能的机制HF刺激传导阻滞的神经元，并提供深入了解HF刺激对神经网络的影响。
High-frequency (HF) stimulation has been shown to block conduction in excitable cells including neurons and cardiac myocytes. However, the precise mechanisms underlying conduction block are unclear. Using a multi-scale method, the influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation alters the amplitude and frequency of repetitive firing in response to a constant applied current and increases the threshold to evoke a single action potential in response to a brief applied current pulse. Further, the excitable cells cannot evoke a single action potential or fire repetitively above critical values for the HF stimulation amplitude. Analytical expressions for the critical values and thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley model, it is shown that HF stimulation alters the dynamics of ionic current gating, shifting the steady-state activation, inactivation, and time constant curves, suggesting several possible mechanisms for conduction block. Finally, we demonstrate that HF stimulation of a network of neurons reduces the electrical activity firing rate, increases network synchronization, and for a sufficiently large HF stimulation, leads to complete electrical quiescence. In this study, we demonstrate a novel approach to investigate HF stimulation in biophysically-detailed ionic models of excitable cells, demonstrate possible mechanisms for HF stimulation conduction block in neurons, and provide insight into the influence of HF stimulation on neural networks.
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