A model for amplification of hair-bundle motion by cyclical binding of Ca2+ to mechanoelectrical-transduction channels
A model for amplification of hair-bundle motion by cyclical binding of Ca2+ to mechanoelectrical-transduction channels
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DOI：
10.1073/pnas.95.26.15321
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发表时间：
1998-12-22
影响因子：
11.1
通讯作者：
Hudspeth, AJ
中科院分区：
文献类型：
--
作者：
Choe, Y;Magnasco, MO;Hudspeth, AJ
毛细胞对听觉刺激的放大增强了脊椎动物内耳的敏感性。外毛细胞的细胞体收缩被认为介导哺乳动物耳蜗的放大。在缺乏这些细胞的脊椎动物中，或许在哺乳动物中也是如此，发束的主动运动可能是放大的基础。我们评估了一个数学模型，其中放大源于机电传导通道的活动。 Ca2+ 与通道的细胞内结合可促进通道关闭，从而增加门控弹簧的张力并对发束施加负力。通过增强束运动，该力部分补偿耳蜗液的粘性阻尼。六态动力学模型的线性稳定性分析揭示了生理范围内参数值的 Hopf 分岔。这些分岔表示系统行为从阻尼振荡响应变为自发极限环振荡的条件。通过改变束中静纤毛的数量和 Ca2+ 结合的速率常数，我们计算了跨越代表性受体器官（鸡的耳蜗）听觉敏感性观察范围的分叉频率。使用预分岔参数值的模拟证明了具有显着压缩非线性的频率选择性放大。由于转导通道普遍存在于毛细胞中，因此这种主动通道模型描述了一种可能适用于跨物种和毛细胞类型的听觉放大机制。
Amplification of auditory stimuli by hair cells augments the sensitivity of the vertebrate inner ear. Cell-body contractions of outer hair cells are thought to mediate amplification in the mammalian cochlea. In vertebrates that lack these cells, and perhaps in mammals as well, active movements of hair bundles may underlie amplification. We have evaluated a mathematical model in which amplification stems from the activity of mechanoelectrical-transduction channels. The intracellular binding of Ca2+ to channels is posited to promote their closure, which increases the tension in gating springs and exerts a negative force on the hair bundle. By enhancing bundle motion, this force partially compensates for viscous damping by cochlear fluids. Linear stability analysis of a six-state kinetic model reveals Hopf bifurcations for parameter values in the physiological range. These bifurcations signal conditions under which the system's behavior changes from a damped oscillatory response to spontaneous limit-cycle oscillation. By varying the number of stereocilia in a bundle and the rate constant for Ca2+ binding, we calculate bifurcation frequencies spanning the observed range of auditory sensitivity for a representative receptor organ, the chicken's cochlea. Simulations using prebifurcation parameter values demonstrate frequency-selective amplification with a striking compressive nonlinearity. Because transduction channels occur universally in hair cells, this active-channel model describes a mechanism of auditory amplification potentially applicable across species and hair-cell types.