Model Analysis of Post-Stimulation Effect on Axonal Conduction and Block.
Model Analysis of Post-Stimulation Effect on Axonal Conduction and Block.
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DOI：
10.1109/tbme.2021.3057522
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Tai C
中科院分区：
文献类型：
--
作者：
Zhong Y;Wang J;Beckel J;de Groat WC;Tai C
揭示膜离子浓度梯度和离子泵活性变化在长时间电刺激诱导的轴突传导/阻断中的可能作用。基于经典的Hodgkin-Huxley(HH)方程建立了一个新的无髓轴突传导和阻断模型，该模型考虑了Na+、K+浓度和离子泵的变化。利用该模型通过计算机模拟分析了长时间刺激对轴突传导/阻断的影响。新模型成功地模拟了由短持续时间(数毫秒)刺激引起的动作电位的启动、传播和阻断，这些刺激不会显著改变经典HH模型中的离子浓度。此外，新模型还成功地模拟了动物实验中观察到的活动依赖效应，如动作电位的衰减和展宽。最后，该模型成功地模拟了最近动物研究中观察到的长时间(数秒)直流电刺激终止后发生的轴突传导阻滞，并揭示了直流电刺激后轴突传导阻滞的三种不同机制。离子浓度和泵在轴突传导/阻断的刺激后效应和活动依赖性效应中起重要作用。刺激的持续时间是一个决定性因素，因为它影响施加到轴突的总电荷，这反过来又决定了轴突内外的离子浓度。尽管最近许多神经刺激疗法在临床上取得了成功，但长时间刺激对轴突传导/阻断的影响尚不清楚。这一新模型可能会显著影响我们对不同神经刺激疗法背后的机制的理解。
To reveal the possible contribution of changes in membrane ion concentration gradients and ion pump activity to axonal conduction/block induced by long-duration electrical stimulation. A new model for conduction and block of unmyelinated axons based on the classical Hodgkin-Huxley (HH) equations is developed to include changes in Na+ and K+ concentrations and ion pumps. The effect of long-duration stimulation on axonal conduction/block is analyzed by computer simulation using this new model. The new model successfully simulates initiation, propagation, and block of action potentials induced by short-duration (multiple milliseconds) stimulations that do not significantly change the ion concentrations in the classical HH model. In addition, the activity-dependent effects such as action potential attenuation and broadening observed in animal studies are also successfully simulated by the new model. Finally, the model successfully simulates axonal block occurring after terminating a long-duration (multiple seconds) direct current (DC) stimulation as observed in recent animal studies and reveals 3 different mechanisms for the post-DC block of axonal conduction. Ion concentrations and pumps play an important role in post-stimulation effects and activity-dependent effects on axonal conduction/block. The duration of stimulation is a determinant factor because it influences the total charges applied to the axon, which in turn determines the ion concentrations inside and outside the axon. Despite recent clinical success of many neurostimulation therapies, the effects of long-duration stimulation on axonal conduction/block are poorly understood. This new model could significantly impact our understanding of the mechanisms underlying different neurostimulation therapies.