论文标题

对非线性电容的Prestin真实和虚构组件的频率响应的状态依赖性影响

State dependent effects on the frequency response of prestin real and imaginary components of nonlinear capacitance

论文作者

Santos-Sacchi, Joseph, Navaratnam, Dhasakumar, Tan, Winston

论文摘要

外毛细胞(OHC)膜具有高密度的电压依赖性蛋白Prestin(SLC26A5),其电荷运动被证明是非线性电容(NLC)。 NLC是钟形的,其峰出现在电压VH上,其中传感器电荷在整个质膜上平均分布。因此,VH提供了有关普雷斯汀构象状态的信息。 VH对膜张力很敏感,随着张力的增加而转移到正电压,是考虑Prestin Piezoelectric(PZE)的基础。可以将NLC解构为真实和虚构的组件,这些组件报告相位的电荷运动或与交流电压相位90度。在这里,我们在OHC的膜宏观斑点上表明,随着审讯频率的增加,实际和虚构成分的部分取舍,如最近的PZE模型所预测的那样(Rabbitt,2020)。但是,我们在Prestin的简单动力学模型中发现了类似的行为,该模型缺乏压电耦合Meno Presto模型。在特定的频率下,FIS,复杂的成分相交。使用此指标,FIS取决于每个复合物分量的频率响应,我们发现初始VH会影响FIS;因此,通过将斑块分为不同VH的组(以上和低于-30 mV),我们发现负VH组的FIS较低。我们还发现,膜张力对复杂NLC的影响取决于初始VH,但差异化。负面群体表现出较高的张力频率,而正面的张力则相反。尽管组件取舍了复杂的成分,但NLC绝对幅度的低通滚减,这与我们的扰动差异很小,并且表明总电荷运动减少,这对电压驱动的Prestin在非常高的频率下的耳蜗放大中的作用构成了挑战。

The outer hair cell (OHC) membrane harbors a voltage-dependent protein, prestin (SLC26a5), in high density, whose charge movement is evidenced as a nonlinear capacitance (NLC). NLC is bell-shaped, with its peak occurring at a voltage, Vh, where sensor charge is equally distributed across the plasma membrane. Thus, Vh provides information on the conformational state of prestin. Vh is sensitive to membrane tension, shifting to positive voltage as tension increases and is the basis for considering prestin piezoelectric (PZE). NLC can be deconstructed into real and imaginary components that report on charge movements in phase or 90 degrees out of phase with AC voltage. Here we show in membrane macro-patches of the OHC that there is a partial trade-off in the magnitude of real and imaginary components as interrogation frequency increases, as predicted by a recent PZE model (Rabbitt, 2020). However, we find similar behavior in a simple kinetic model of prestin that lacks piezoelectric coupling, the meno presto model. At a particular frequency, Fis, the complex component magnitudes intersect. Using this metric, Fis, which depends on the frequency response of each complex component, we find that initial Vh influences Fis; thus, by categorizing patches into groups of different Vh, (above and below -30 mV) we find that Fis is lower for the negative Vh group. We also find that the effect of membrane tension on complex NLC is dependent, but differentially so, on initial Vh. Whereas the negative group exhibits shifts to higher frequencies for increasing tension, the opposite occurs for the positive group. Despite complex component trade-offs, the low-pass roll-off in absolute magnitude of NLC, which varies little with our perturbations and is indicative of diminishing total charge movement, poses a challenge for a role of voltage-driven prestin in cochlear amplification at very high frequencies.

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