Dynamics and sensitivity analysis of high-frequency conduction block.
Dynamics and sensitivity analysis of high-frequency conduction block.
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高频传导块的动力学和灵敏度分析。
DOI：
10.1088/1741-2560/8/6/065007
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发表时间：
2011-12
影响因子：
4
通讯作者：
Thomas PJ
中科院分区：
文献类型：
--
作者：
Ackermann DM;Bhadra N;Gerges M;Thomas PJ
细胞外高频刺激（HFS）的局部递送已被证明是阻断神经传导的快速作用和快速可逆的方法，并且目前正在寻求用于几种临床适应症。然而，这种类型的神经阻滞的机制仍不清楚。在这项研究中，我们调查了两个假设：1）去极化电流通过钠通道失活促进传导阻滞，2）快钠通道的门控动力学是最小阻滞频率的主要决定因素。假设1采用模型和实验相结合的方法研究去极化和超极化电流对高频阻滞的影响。建模研究的结果表明，去极化和超极化电流在传导阻滞中起着重要作用，并且在HFS期间，三种离子电流中的每一种的电导相对于静息值增加。然而，去极化电流被发现，以促进阻断效果，和超极化电流被发现，以减少阻断效果。内向钠电流大于外向电流的总和，导致结膜的净去极化。我们的实验结果支持这些发现，并密切匹配的结果，从等效的建模方案：腹膜内给药的持久性钠通道阻滞剂雷诺嗪导致HFS的幅度增加所需的大鼠产生传导阻滞，证实去极化电流促进传导阻滞现象。假设2使用单纤维轴突模型中的通道门控变量的谱分析进行了研究。这项研究的结果表明，特定的离子通道门控元件的动力学性质和相应的电导阻断发作的贡献之间的关系。具体来说，我们表明，快速钠失活门的动力学太慢，无法跟踪高频的膜电位变化在HFS，和快速钠电流的行为是由低频去极化的膜。结果，在阻断状态下，在最接近阻断电极的节点中，发现只有5.4%的节点钠通道处于可激活状态，导致传导阻滞。此外，我们发现，持续性钠通道激活门的转角频率对应于任意振幅的高频刺激不能诱导传导阻滞的频率。
The local delivery of extracellular high frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction, and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: 1) That depolarizing currents promote conduction block via inactivation of sodium channels, and 2) that the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in a conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high frequency stimuli of arbitrary amplitude are incapable of inducing conduction block.
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影响因子：
3
作者：
Foldes, Emily L.;Ackermann, D. Michael;Bhadra, Niloy;Kilgore, Kevin L.;Bhadra, Narendra
通讯作者：
Bhadra, Narendra
影响因子：
5.5
作者：
Cattell, M;Gerard, RW
通讯作者：
Gerard, RW
影响因子：
3.4
作者：
Bhadra, N;Kilgore, KL
通讯作者：
Kilgore, KL
神经袖带电极几何形状对高频神经传导阻滞中起始反应放电的影响。
DOI：
10.1109/tnsre.2010.2071882
发表时间：
2010-12
期刊：
IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society
影响因子：
--
作者：
Ackermann DM Jr;Bhadra N;Foldes EL;Wang XF;Kilgore KL
通讯作者：
Kilgore KL
影响因子：
1.6
作者：
Gould HJ 3rd;Garrett C;Donahue RR;Paul D;Diamond I;Taylor BK
通讯作者：
Taylor BK