Fransén Erik, Alonso Angel A, Dickson Clayton T, Magistretti Jacopo, Hasselmo Michael E
Department of Numerical Analysis and Computer Science, Royal Institute of Technology, Stockholm, Sweden.
Hippocampus. 2004;14(3):368-84. doi: 10.1002/hipo.10198.
A multicompartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I(Nap)) and the hyperpolarization activated inward current (Ih) in the generation of subthreshold membrane potential oscillations. The potential role of Ih in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of Ih and the slow calcium-activated potassium current Ikappa(AHP) in action potential clustering was also studied. Representations of Ih and I(Nap) were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et al., J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of Ih with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of Ih does not follow the fast component down to very short time constants. The model also predicts that the fast component of Ih is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters.
构建了一个内嗅皮层II层星状细胞的多室生物物理模型,以分析生理特性的离子基础,如阈下膜电位振荡、动作电位簇集和中等后超极化。具体而言,该模拟说明了持续性钠电流(I(Nap))和超极化激活内向电流(Ih)在阈下膜电位振荡产生中的相互作用。研究了Ih在中等超极化(mAHP)和反弹放电中的潜在作用。还研究了Ih和慢钙激活钾电流Ikappa(AHP)在动作电位簇集中的作用。Ih和I(Nap)的表征是根据来自星状细胞全细胞膜片钳和单通道记录的电压钳数据的参数构建的(Dickson等人,《神经生理学杂志》83:2562 - 2579,2000;Magistretti和Alonso,《普通生理学杂志》114:491 - 509,1999;Magistretti等人,《生理学杂志》521:629 - 636,1999a;《神经科学杂志》19:7334 - 7341,1999b)。这些电流相互作用,产生了幅度和频率与全细胞膜片钳记录中观察到的数据相对应的强大阈下膜电位。该模型还能够解释药理学操作的影响,包括用ZD7288阻断Ih、用铯部分阻断以及钡对振荡的影响。在一个具有更广泛电流范围的模型中,可以复制从振荡到单个放电、到放电簇集,最终到强直性放电的转变。与实验一致,模型中钙通道的阻断强烈减少了簇集。在没有数据的电压区间内,该模型预测Ih的慢成分不会跟随快成分下降到非常短的时间常数。该模型还预测Ih的快成分参与阈下振荡的产生,而慢成分在放电簇集的产生中占主导地位。