A physiologically based model of discharge pattern regulation by transient K+ currents in cochlear nucleus pyramidal cells

A physiologically based model of discharge pattern regulation by transient K+ currents in cochlear nucleus pyramidal cells
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DOI:
10.1152/jn.2001.85.2.523
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发表时间:
2001-02-01
影响因子:
2.5
通讯作者:
Manis, PB
Manis, PB
中科院分区:
医学3区
文献类型:
--
作者:
Kanold, PO;Manis, PB

文献摘要

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耳蜗背核(DCN)锥体细胞在反应音中表现出三种特征性放电模式:暂停放电、累积放电和规则放电。实验证据表明,快速失活K+电流(I-KIF)在产生这些放电模式中起着关键作用。为了探索I-KIF的作用,我们使用了基于生物物理数据的计算模型。该模型复制的依赖性的放电模式的幅度和持续时间的超极化预脉冲,和I-KIF是必要的传达这种依赖性。相平面和微扰分析表明,去极化的反应是严格控制的I-KIF的失活量。在实验上,I-KIF的半失活电压和动力学表现出广泛的可变性。在模型中改变这些参数显示,半失活电压,激活和失活率,控制模型电池放电的电压和时间依赖性。这表明锥体细胞可以通过调节I-KIF的动力学来调节它们对不同时间模式的抑制和兴奋的敏感性。总体而言,I-KIF是控制DCN锥体细胞兴奋性的关键电导。
Pyramidal cells in the dorsal cochlear nucleus (DCN) show three characteristic discharge patterns in response tones: pauser, buildup, and regular firing. Experimental evidence suggests that a rapidly inactivating K+-current (I-KIF) plays a critical role in generating these discharge patterns. To explore the role of I-KIF, we used a computational model based on the biophysical data. The model replicated the dependence of the discharge pattern on the magnitude and duration of hyperpolarizing prepulses, and I-KIF was necessary to convey this dependence. Phase-plane and perturbation analyses show that responses to depolarization are critically controlled by the amount of inactivation of I-KIF. Experimentally, half-inactivation voltage and kinetics of I-KIF show wide variability. Varying these parameters in the model revealed that half-inactivation voltage, and activation and inactivation rates, controls the voltage and time dependence of the model cell discharge. This suggests that pyramidal cells can adjust their sensitivity to different temporal patterns of inhibition and excitation by modulating the kinetics of I-KIF. Overall, I-KIF is a critical conductance controlling the excitability of DCN pyramidal cells.