Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells

Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells
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DOI:
10.1529/biophysj.106.100834
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发表时间:
2007-09-01
影响因子:
3.4
通讯作者:
Iwasa, K. H.
Iwasa, K. H.
中科院分区:
生物学3区
文献类型:
--
作者:
Fang, Jie;Iwasa, K. H.

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外毛细胞细胞体的运动活动与大的非线性电容有关,这是由于膜马达将电位移与膜面积的变化耦合在一起,类似于压电。这种马达是基于prestin, SLC26阴离子转运蛋白家族的一员,并利用与这些细胞的感觉功能相关的质膜上可用的电能。为了了解这种运动活性的详细机制,我们研究了两性离子、阳离子氯丙嗪和阴离子三硝基酚的作用,它们被认为是在相反的方向上改变膜的曲率。我们发现这两种化学物质在保持电位为-75 mV时都缩短了电池的长度,并诱导了电池电压依赖性的正变化。观察到的位移与500 mM三硝基苯酚的10 mV和100 μ M阳离子氯丙嗪的20 mV相似。保持电位的长度减少与运动活动的电压变化有很好的相关性。消除细胞的胀压或消化皮质细胞骨架并不能降低非线性电容的电压位移。这些观察结果表明,膜马达经历构象转变,不仅涉及膜面积的变化,而且涉及弯曲刚度的变化。
The motile activity of outer hair cells' cell body is associated with large nonlinear capacitance due to a membrane motor that couples electric displacement with changes in the membrane area, analogous to piezoelectricity. This motor is based on prestin, a member of the SLC26 family of anion transporters and utilizes the electric energy available at the plasma membrane associated with the sensory function of these cells. To understand detailed mechanism of this motile activity, we examined the effect of amphipathic ions, cationic chlorpromazine and anionic trinitrophenol, which are thought to change the curvature of the membrane in opposite directions. We found that both chemicals reduced cell length at the holding potential of -75 mV and induced positive shifts in the cells' voltage dependence. The shift observed was similar to 10 mV for 500 mM trinitrophenol and 20 mV for 100 mu M cationic chlorpromazine. Length reduction at the holding potential and voltage shifts of the motile activity were well correlated. The voltage shifts of nonlinear capacitance were not diminished by eliminating the cells' turgor pressure or by digesting the cortical cytoskeleton. These observations suggest that the membrane motor undergoes conformational transitions that involve changes not only in membrane area but also in bending stiffness.