Investigations of Bio Markers for ion channel activities on insulinoma cells

Ruiguo Yang, N. Xi, K. Lai, C. Fung, Chengeng Qu, Beihua Zhong, Donna H. Wang
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引用次数: 1

Abstract

Ion channel is the regulatory mechanism for electrical activity in pancreatic islet cells through stimulus-secretion coupling. Changes in membrane potential are regulated by the glucose concentration-dependent ion channel activities. The alteration of glucose concentration is linked to the open probability of ATP-sensitive K+ channels by insulin secretion. At the meantime, the change of glucose concentration can cause the reorganization of the membrane as well as the cytoskeleton, resulting in the change of cellular stiffness. By using an integrated AFM and cell manipulation system, we were able to measure the cell stiffness and structural change simultaneously upon the glucose stimulation. The cell stiffness increases substantially in a dosage-dependent manner after stimulation by real time AFM nanoindentation measurement. Structurally, the cell height decrease dynamically with the glucose concentration increase. Therefore we have a unique Bio Marker to characterize the ion channel activity using different modalities. This result indicates that the open and close of ion channel would lead to the change of membrane structure and thus the cell body exhibits a different cellular stiffness. The study will enhance our understanding of pancreatic islet cell stimulus coupling and insulin secretion.
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胰岛素瘤细胞离子通道活性生物标志物的研究
离子通道是胰岛细胞电活动通过刺激-分泌耦合的调节机制。膜电位的变化受葡萄糖浓度依赖性离子通道活性的调节。葡萄糖浓度的改变与胰岛素分泌导致atp敏感的K+通道打开的可能性有关。同时,葡萄糖浓度的变化会引起细胞膜和细胞骨架的重组,从而导致细胞刚度的改变。通过集成AFM和细胞操作系统,我们能够同时测量葡萄糖刺激下的细胞刚度和结构变化。在实时AFM纳米压痕测量刺激后,细胞刚度以剂量依赖的方式显著增加。在结构上,细胞高度随葡萄糖浓度的增加而动态降低。因此,我们有一个独特的生物标记来表征离子通道活性使用不同的模式。这表明离子通道的打开和关闭会引起膜结构的变化,从而使细胞体表现出不同的细胞刚度。该研究将加深我们对胰岛细胞刺激偶联和胰岛素分泌的认识。
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