Wu Y C, Fettiplace R
Department of Neurophysiology, University of Wisconsin Medical School, Madison 53706, USA.
Biophys J. 1996 Jun;70(6):2557-70. doi: 10.1016/S0006-3495(96)79827-2.
Hair cells in the turtle cochlea are frequency-tuned by a mechanism involving the combined activation of voltage-sensitive Ca2+ channels and Ca(2+)-activated K+ (KCa) channels. The main determinants of a hair cell's characteristic frequency (Fo) are the KCa channels' density and kinetics, both of which change systematically with location in the cochlea in conjunction with the observed frequency map. We have developed a model based on the differential expression of two KCa channel subunits, which when accompanied by concurrent changes in other properties (e.g., density of Ca2+ channels and inwardly rectifying K+ channels), will generate sharp tuning at frequencies from 40 to 600 Hz. The kinetic properties of the two subunits were derived from previous single-channel analysis, and it was assumed that the subunits (A and B) combine to form five species of tetrameric channel (A4, A3B, A2B2, AB3, and B4) with intermediate kinetics and overlapping distribution. Expression of KCa and other channels was assumed to be regulated by diffusional gradients in either one or two chemicals. The results are consistent with both current- and voltage-clamp data on turtle hair cells, and they show that five channel species are sufficient to produce smooth changes in both Fo and kinetics of the macroscopic KCa current. Other schemes for varying KCa channel kinetics are examined, including one that allows extension of the model to the chick cochlea to produce hair cells with Fo's from 130 to 4000 Hz. A necessary assumption in all models is a gradient in the values of the parameters identified with the cell's cytoplasmic Ca2+ buffer.
乌龟耳蜗中的毛细胞通过一种涉及电压敏感Ca2+通道和Ca(2+)-激活K+（KCa）通道联合激活的机制进行频率调谐。毛细胞特征频率（Fo）的主要决定因素是KCa通道的密度和动力学，这两者都随着耳蜗中的位置而系统地变化，并与观察到的频率图相关联。我们基于两种KCa通道亚基的差异表达开发了一个模型，当该模型伴随着其他特性（例如Ca2+通道和内向整流K+通道的密度）的同时变化时，将在40至600Hz的频率下产生尖锐的调谐。这两个亚基的动力学特性来自先前的单通道分析，并且假设亚基（A和B）组合形成五种四聚体通道（A4、A3B、A2B2、AB3和B4），具有中间动力学和重叠分布。假设KCa通道和其他通道的表达受一种或两种化学物质中的扩散梯度调节。结果与乌龟毛细胞的电流钳和电压钳数据一致，并且表明五种通道类型足以在宏观KCa电流的Fo和动力学方面产生平滑变化。研究了改变KCa通道动力学的其他方案，包括一种允许将模型扩展到鸡耳蜗以产生Fo为130至4000Hz的毛细胞的方案。所有模型中的一个必要假设是与细胞胞质Ca2+缓冲液相关的参数值存在梯度。
