Impulse encoding mechanisms of ganglion cells in the tiger salamander retina
Impulse encoding mechanisms of ganglion cells in the tiger salamander retina
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DOI：
10.1152/jn.1997.78.4.1935
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发表时间：
1997-10-01
影响因子：
2.5
通讯作者：
Miller, RF
中科院分区：
文献类型：
--
作者：
Fohlmeister, JF;Miller, RF
采用实验与分析相结合的方法，包括基于单室模型的计算机模拟，对虎蝾螈视网膜神经节细胞的神经冲动产生进行了研究。使用视网膜-眼杯制备获得神经节细胞的全细胞记录，并使用药理学和电生理技术进行研究，包括相图分析。实验工作是通过计算机模拟研究一个由五个电压或离子门控通道组成的兴奋性模型来指导的，这些通道是从早期的电压箝位数据中确定的。离子通道包括钠离子、钙离子和三种钾离子通道，即A型（I-K、I-A）、钙活化钾离子（I-K、I-Ca）和延迟整流离子（I-K）。为了保持模型和实验之间的输入电阻连续性，设计了泄漏通道。单室模型中Na和Ca电流（I-Na和I-Ca）的离子通道密度由相图分析独立确定。根据测量的脉冲宽度确定了I-K和I-K，I-A电流密度。模拟I-K、I-Ca对Ca内流的响应，并采用可变速率的Ca螯合机制去除细胞质钙。在全细胞记录实验中，当I-Ca或I-K、I-Ca从模型中消除或被药理学阻断时，脉冲频率增加。实验数据的忠实模拟表明，离子电流可以分为小（I-K,I-Ca，泄漏和刺激）和大（I-Na, I-K, I-A, I-Ca）在脉冲序列的基础上，他们的峰值幅度。电流的这种划分反映在它们控制尖峰间隔（小电流）和脉冲产生（大电流）的功能上。尽管单室模型在定性上成功地模拟了脉冲频率行为及其控制机制，但发现了一些局限性，特别是需要包括形态学细节。尖峰序列分析指出了电紧张电流在控制尖峰间隔持续时间中的作用，这可以通过单室模型中g（K,Ca）的延长激活来补偿。一个详细的，多室模型的神经节细胞提出了在配套文件。
A study of nerve impulse generation in ganglion cells of the tiger salamander retina is carried out through a combination of experimental and analytic approaches, including computer simulations based on a single-compartment model. Whole cell recordings from ganglion cells were obtained using a superfused retina-eyecup preparation and studied with pharmacological and electrophysiological techniques, including phase plot analysis. Experimental efforts were guided by computer simulation studies of an excitability model consisting of five voltage-or ion-gated channels, which were identified from earlier voltage-clamp data. The ion channels include sodium, calcium, and three types of potassium channels, namely the A type (I-K,I-A), Ca-activated potassium (I-K,I-Ca), and the delayed rectifier (I-K). A leakage channel was included to preserve input resistance continuity between model and experiment. Ion channel densities of Na and Ca currents (I-Na and I-Ca) for the single-compartment model were independently determined from phase plot analysis. The I-K and I-K,I-A current densities were determined from the measured width of impulses. The I-K,I-Ca was modeled to respond to Ca influx, and a variable-rate Ca-sequestering mechanism was implemented to remove cytoplasmic calcium. Impulse frequency increases when either I-Ca or I-K,I-Ca is eliminated from the model or blocked pharmacologically in whole cell recording experiments. Faithful simulations of experimental data show that the ionic currents may be grouped into small (I-K,I-Ca, leakage, and stimulus), and large (I-Na, I-K, I-A, I-Ca) on the basis of their peak magnitudes throughout the impulse train. This division of the currents is reflected in their function of controlling the interspike interval (small currents) and impulse generation (large currents rents). Although the single-compartmental model is qualitatively successful in simulating impulse frequency behavior and its controlling mechanisms, limitations were found that specifically suggest the need to include morphological details. The spike train analysis points to a role for electrotonic currents in the control of the duration of the interspike intervals, which can be compensated by prolonged activation of g(K,Ca) in the single-compartment model. A detailed, multicompartmental model of the ganglion cell is presented in the companion paper.