Lundbaek J A, Birn P, Girshman J, Hansen A J, Andersen O S
Department of Physiology and Biophysics, Cornell University Medical College, New York, New York 10021, USA.
Biochemistry. 1996 Mar 26;35(12):3825-30. doi: 10.1021/bi952250b.
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.
脂质双层刚度的改变可能构成调节膜蛋白功能的一种普遍机制。短杆菌肽通道可用作分子力传感器来测量双层刚度的此类变化。作为一种应用，我们表明，降低双层刚度的合成洗涤剂可使N型钙通道失活向负电位方向可逆性偏移。增加双层刚度的胆固醇则使通道失活向正电位方向偏移。钙通道的电压激活不受刚度变化的影响。双层刚度的变化可根据膜活性化合物的分子形状来预测，这为此类化合物的药理作用提供了一个依据。
