SIMULATION OF THE CURRENTS INVOLVED IN RHYTHMIC OSCILLATIONS IN THALAMIC RELAY NEURONS
SIMULATION OF THE CURRENTS INVOLVED IN RHYTHMIC OSCILLATIONS IN THALAMIC RELAY NEURONS
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DOI：
10.1152/jn.1992.68.4.1373
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发表时间：
1992-10-01
影响因子：
2.5
通讯作者：
MCCORMICK, DA
中科院分区：
文献类型：
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作者：
HUGUENARD, JR;MCCORMICK, DA
1. 为了模拟丘脑继电器神经元中动作电位产生的各种模式，我们开发了霍奇金和赫胥黎风格的数学方程，描述了四种不同电流的电压依赖性和激活和失活动力学，包括瞬态低压激活的Ca2+电流（I(T)），快速失活的瞬态K+电流（I(A)），缓慢失活的K+电流（I(K2)），以及超极化激活的，混合阳离子电流I(h)。模型电流来源于急性分离的大鼠丘脑接力神经元(I(T)， I(A)， I(K2))，或来自体外切片保存的豚鼠丘脑接力细胞（I(h)）。I(T)、I(A)和I（K2）的稳态激活和失活以及I(h)的激活的电压依赖关系可以用玻尔兹曼式方程来建模。模拟电压钳中I(T)对去极化步骤的行为需要使用常场方程来将磁导率与T电流幅度联系起来。I(T)的激活时间常数是一个连续的钟形函数，在激活阈值（-75 mV）和23℃时最大在15 ms附近。失活动力学的数学描述和消除该电流的失活需要两个单独的函数。通过假设两种不同失活时间常数的组分，对K+电流I(A)的快速激活和失活进行了建模。激活动力学被描述为电压的连续函数，在激活阈值（-60 mV）和23℃时，时间常数最慢，接近2.5 ms。相反，这两种组分的失活动力学被描述为与电压无关，与实验数据一致。I(A)两组分失活的速率或去除率随超极化程度的增加而不断增加。缓慢失活的K+电流I（K2）也通过假设两种不同失活速率的组分来建模。活化动力学描述为钟形函数，在-40 mV和23℃下，最大时间常数接近80 ms，而活化阈值约为-60 mV。这两种成分的失活被建模为相对独立于电压，而失活的去除被描述为膜电位的连续函数。超极化活化阳离子电流I(h)是通过假设电流以单指数关系激活而不灭活来建模的。I(h)的激活和失活动力学由膜电位的连续钟形函数描述，最慢的激活速率（35℃时时间常数约为1 s）发生在-80 mV，接近半激活的膜电位（-75 mV）。对I(T)、I(A)、I（K2）和I(h)这四种电流的电压依赖性、动力学和反转电位的分析和建模预测，I(T)应该提供内向电流或产生低阈值Ca2+尖峰，快速激活和灭活的K+电流I(A)调节这些Ca2+尖峰的初始成分。相比之下，K+电流I（K2）的激活和失活的较慢动力学表明，该电流可能更多地影响低阈值Ca2+峰值的后期部分。I(h)的性质表明，它对细胞在超极化膜电位下的电压-时间过程的调节至关重要，并可能为节律性突发的产生提供“起搏器”电位。
1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (I(T)), the rapidly inactivating transient K+ current (I(A)), the slowly inactivating K+ current (I(K2)), and the hyperpolarization-activated, mixed cationic current (I(h)). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (I(T), I(A), I(K2)), or from guinea pig thalamic relay cells maintained in slices in vitro (I(h)).2. The voltage dependence of steady-state activation and inactivation of I(T), I(A), and I(K2) and the activation of I(h) could be modeled with Boltzmann-style equations. Modeling of the behavior of I(T) to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of I(T) was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23-degrees-C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions.3. The rapidly activating and inactivating K+ current I(A) was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23-degrees-C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of I(A) was described as continuously increasing with the degree of hyperpolarization.4. The slowly inactivating K+ current I(K2) was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23-degrees-C, whereas threshold for activation was approximately -60 mV. InActivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential.5. The hyperpolarization-activation cationic current, I(h), was modeled by assuming that the current activates with a single exponential relation and does not inactivate. The kinetics of activation and deactivation of I(h) were described by a continuous and bell-shaped function of membrane potential, with the slowest rate of activation (time constant of approximately 1 s at 35-degrees-C) occurring at -80 mV, which is near the membrane potential for half activation (-75 mV).6. The analysis and modeling of the voltage dependence, kinetics, and reversal potentials of these four currents, I(T), I(A), I(K2), and I(h), predict that I(T) should provide the inward current or generation of low-threshold Ca2+ spikes, with the rapidly activating and inactivating K+ current I(A) modulating the initial components of these Ca2+ spikes. In contrast, the slower kinetics of activation and inactivation of the K+ current I(K2) suggest that this current may affect more the later portions of low-threshold Ca2+ spikes. The properties of I(h) suggest that it is critical to modulation of the voltage-time course of the cell at hyperpolarized membrane potentials and may provide a "pacemaker" potential for rhythmic burst generation.