Biological membranes carry fixed charges at their surfaces. These arise primarily from phospholipid headgroups. In addition, membrane proteins contribute to the surface potential with their charged residues. Membrane lipids are asymmetrically distributed. Because of this asymmetry, the net-negative charge at the inner leaflet exceeds that at the outer leaflet. Changes in surface potential are predicted to give rise to apparent changes in membrane capacitance. Here, we show that it is possible to detect changes in surface potential by an electrophysiological approach; the analysis of cellular currents relies on assuming that the electrical properties of a cell are faithfully described by a three-element circuit (i.e., the minimal equivalent circuit) comprised of two resistors and one capacitor. However, to account for changes in surface potential, it is necessary to add a battery to this circuit connected in series with the capacitor. This extended circuit model predicts that the current response to a square-wave voltage pulse harbors information, which allows for separating the changes in surface potential from a true capacitance change. We interrogated our model by investigating changes in the capacitance induced by ligand binding to the serotonin transporter and to the glycine transporters (GlyT1 and GlyT2). The experimental observations were consistent with the predictions of the extended circuit. We conclude that ligand-induced changes in surface potential (reflecting the binding event) and in true membrane capacitance (reflecting the concomitant conformational change) can be detected in real time even in instances in which they occur simultaneously.

中文翻译：

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一种实时测量膜表面电位变化的电生理方法

生物膜在其表面带有固定电荷。这些主要来自磷脂头基。此外，膜蛋白通过其带电残基对表面电位有贡献。膜脂质不对称分布。由于这种不对称性，内小叶的净负电荷超过外小叶的净负电荷。预计表面电位的变化会引起膜电容的明显变化。在这里，我们表明可以通过电生理学方法检测表面电位的变化；细胞电流的分析依赖于假设细胞的电特性由由两个电阻器和一个电容器组成的三元件电路（即最小等效电路）忠实地描述。然而，为了说明表面电位的变化，需要在与电容器串联的电路中添加电池。该扩展电路模型预测，对方波电压脉冲的电流响应包含信息，这允许将表面电位的变化与真实的电容变化分开。我们通过研究配体与血清素转运蛋白和甘氨酸转运蛋白（GlyT1 和 GlyT2）结合引起的电容变化来询问我们的模型。实验观察与扩展电路的预测一致。我们得出结论，即使在它们同时发生的情况下，也可以实时检测配体诱导的表面电位变化（反映结合事件）和真实膜电容（反映伴随的构象变化）。