Institute for Analysis and Scientific Computing, Vienna University of Technology , Vienna , Austria.
J Neurophysiol. 2019 Apr 1;121(4):1315-1328. doi: 10.1152/jn.00700.2018. Epub 2019 Feb 6.
Exceeding a certain stimulation strength can prevent the generation of somatic action potentials, as has been demonstrated in vitro with extracellularly stimulated dorsal root ganglion cells as well as retinal ganglion cells. This phenomenon, termed upper threshold, is currently thought to be a consequence of sodium current reversal in strongly depolarized regions. Here we analyze the contribution of membrane kinetics, using spherical model neurons that are stimulated externally with a microelectrode, in more detail. During extracellular pulse application, the electric field depolarizes one part and hyperpolarizes the other part of the cell. Strong transmembrane currents are generated only in the active depolarized region, changing the overall polarization level. The asymmetric membrane voltage distribution caused by the stimulus strongly influences the cell's behavior during and even after the stimulus. Effects on membrane voltage and transmembrane currents during and after the stimulus are shown and discussed in detail. Aside from the sodium current reversal, two more key mechanisms were identified in causing the upper threshold: strong potassium currents and inactivation of sodium channels. The contributions of the mechanisms involved strongly depend on cell properties, stimulus parameters, and other factors such as temperature. The conclusions presented here are based on several retinal ganglion cell models of the Fohlmeister group, a model with original Hodgkin-Huxley membrane, and a pyramidal cell model. NEW & NOTEWORTHY The upper threshold phenomenon in extracellular stimulation is analyzed in detail for spherical cells. Three main mechanisms were identified that prevent the generation of action potentials at high stimulation strengths: 1) strong potassium currents, 2) inactivating sodium ion channels, and 3) sodium current reversal. Ion channel kinetics in retinal ganglion cells, pyramidal cells, and the original Hodgkin-Huxley model were investigated under the influence of an extracellular stimulus.
超过一定的刺激强度可以阻止躯体动作电位的产生，这已在体外使用细胞外刺激的背根神经节细胞和视网膜神经节细胞中得到证明。这种现象称为上阈，目前被认为是钠离子电流在强烈去极化区域反转的结果。在这里，我们使用外部刺激的球形模型神经元更详细地分析了膜动力学的贡献。在细胞外脉冲施加期间，电场使细胞的一部分去极化，另一部分超极化。只有在主动去极化区域才会产生强跨膜电流，从而改变整体极化水平。刺激引起的不对称膜电压分布强烈影响细胞在刺激期间甚至刺激后的行为。在刺激期间和刺激后，详细显示和讨论了膜电压和跨膜电流的影响。除了钠离子电流反转之外，还有另外两个关键机制被确定为上阈的原因：强钾电流和钠离子通道失活。所涉及的机制的贡献强烈取决于细胞特性、刺激参数以及其他因素，如温度。这里提出的结论是基于 Fohlmeister 小组的几个视网膜神经节细胞模型、具有原始 Hodgkin-Huxley 膜的模型和一个锥体细胞模型得出的。新的和值得注意的是，详细分析了细胞外刺激中的上阈现象。确定了阻止在高刺激强度下产生动作电位的三个主要机制：1）强钾电流，2）失活的钠离子通道，3）钠离子电流反转。在细胞外刺激的影响下，研究了视网膜神经节细胞、锥体细胞和原始 Hodgkin-Huxley 模型中的离子通道动力学。
