Negm Mohamed H, Bruce Ian C
IEEE Trans Biomed Eng. 2014 Nov;61(11):2749-59. doi: 10.1109/TBME.2014.2327055. Epub 2014 May 29.
An accurate model of auditory nerve fibers (ANFs) may assist in developing improved cochlear implant (CI) stimulation strategies. Previous studies have shown that the original Hodgkin-Huxley (HH) model may be better at describing nodes of Ranvier in ANFs than models for other mammalian axon types. However, the HH model is still unable to explain a number of phenomena observed in auditory nerve responses to CI stimulation such as adaptation to high-rate stimulation and the time course of relative refractoriness. Recent physiological investigations of ANFs have shown the presence of a number of ion channel types not considered in the previous modeling studies, including low-threshold potassium (KLT) channels and hyperpolarization-activated cation (HCN) channels. In this paper, we investigate inclusion of these ion channel types in a stochastic HH model of a single node of Ranvier. Simulation results for pulse trains with rates of 200, 800, and 2000 pulse/s suggests that both the KLT channels and HCN channels can produce adaptation in the spike rate. However, the adaptation due to KLT is restricted to higher stimulation rates, whereas the adaptation due to HCN is observed across all stimulation rates. Additionally, using pulse pairs it was found that KLT increased both the absolute and the relative refractory periods. HCN on its own increased just the relative refractory period, but produced a synergistic increase in the absolute refractory period when combined with KLT. Together these results argue strongly for the need to consider HCN and KLT channels when studying CI stimulation of ANFs.
准确的听神经纤维(ANF)模型可能有助于开发改进的人工耳蜗(CI)刺激策略。先前的研究表明,原始的霍奇金-赫胥黎(HH)模型在描述听神经纤维的郎飞结方面可能比其他哺乳动物轴突类型的模型更好。然而,HH模型仍然无法解释在听神经对CI刺激的反应中观察到的一些现象,例如对高速率刺激的适应以及相对不应期的时间进程。最近对听神经纤维的生理学研究表明,存在许多先前建模研究中未考虑的离子通道类型,包括低阈值钾(KLT)通道和超极化激活阳离子(HCN)通道。在本文中,我们研究了在单个郎飞结的随机HH模型中纳入这些离子通道类型。对速率为200、800和2000脉冲/秒的脉冲序列的模拟结果表明,KLT通道和HCN通道都可以在放电率上产生适应性。然而,KLT引起的适应仅限于较高的刺激速率,而HCN引起的适应在所有刺激速率下都能观察到。此外,使用脉冲对发现,KLT增加了绝对不应期和相对不应期。单独的HCN仅增加了相对不应期,但与KLT结合时会在绝对不应期产生协同增加。这些结果共同有力地表明,在研究人工耳蜗对听神经纤维的刺激时需要考虑HCN和KLT通道。