Membrane stiffness and channel function

Membrane stiffness and channel function
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DOI:
10.1021/bi952250b
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发表时间:
1996-03-26
期刊:
影响因子:
2.9
通讯作者:
Andersen, OS
Andersen, OS
中科院分区:
生物学3区
文献类型:
--
作者:
Lundbaek, JA;Birn, P;Andersen, OS

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脂双层刚性的改变可能构成膜蛋白功能调节的一般机制。Gramiidin通道可用作分子力传感器来测量双分子层硬度的变化。作为应用,我们证明了N型钙通道失活可通过合成洗涤剂降低双层硬度而可逆地向负电位移动,胆固醇增加了双层硬度,使通道失活向正电位移动。钙通道的电压激活不受硬度变化的影响,根据膜活性化合物的分子形状可以预测双分子层硬度的变化,这为此类化合物的药理作用提供了基础。
Alterations in the stiffness of lipid bilayers are likely to constitute a general mechanism for modulation of membrane protein function. Gramicidin channels can be used as molecular force transducers to measure such changes in bilayer stiffness. As an application, we show that N-type calcium channel inactivation is shifted reversibly toward negative potentials by synthetic detergents that decrease bilayer stiffness, Cholesterol, which increases bilayer stiffness, shifts channel inactivation toward positive potentials. The voltage activation of the calcium channels is unaffected by the changes in stiffness, Changes in bilayer stiffness can be predicted from the molecular shapes of membrane-active compounds, which suggests a basis for the pharmacological effects of such compounds.