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瞬时受体电位 melastatin5(TRPM5)通道在胰腺β细胞电活动中的作用:一项计算建模研究。

The role of the transient receptor potential melastatin5 (TRPM5) channels in the pancreatic β-cell electrical activity: A computational modeling study.

机构信息

Department of Medical Physics & Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Medical Physics & Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Computational Nano-Bioelectromagnetics Research Group, School of Nano-Science, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.

出版信息

Comput Biol Chem. 2018 Oct;76:101-108. doi: 10.1016/j.compbiolchem.2018.05.019. Epub 2018 Jun 6.

Abstract

The TRPM5 channels are transient receptor potential channels whose presence in the human pancreatic β-cell has been confirmed. The sensitivity of these channels to membrane voltage, temperature and intracellular calcium concentration and their possible role in insulin secretion has made them a focal point in research in the past decade. While experimental researches have confirmed the role of the TRPM5 channels in insulin secretion, but the underlying mechanism is still unclear. In this study, based on the experimental results of other studies, a mathematical description of the TRPM5 channel activity has been proposed which correlates the TRPM5 electrical activity to the voltage and intracellular calcium concentration. The resulting expression has been added to the existing mathematical model of the human β-cell and the enhanced model has been used for investigating the effect of the TRPM5 channel on the β-cell electrical activity. The results of our study show that the TRPM5 influences other ion channel activities through speeding up membrane depolarization. In addition, we have shown that the TRPM5 increases the amplitude and firing rate of action potentials by possibly affecting the Na and gamma-Aminobutyric acid related currents. The results also confirm the prominent effect of the TRPM5 channels in glucose-stimulated condition.

摘要

TRPM5 通道是瞬时受体电位通道,其在人胰腺 β 细胞中的存在已得到证实。这些通道对膜电压、温度和细胞内钙离子浓度的敏感性及其在胰岛素分泌中的可能作用,使它们成为过去十年研究的焦点。虽然实验研究已经证实了 TRPM5 通道在胰岛素分泌中的作用,但潜在的机制仍不清楚。在这项研究中,基于其他研究的实验结果,我们提出了一种 TRPM5 通道活性的数学描述,将 TRPM5 的电活性与电压和细胞内钙离子浓度相关联。所得表达式已被添加到现有的人类 β 细胞数学模型中,并使用增强模型来研究 TRPM5 通道对 β 细胞电活性的影响。我们的研究结果表明,TRPM5 通过加速膜去极化来影响其他离子通道的活性。此外,我们还表明,TRPM5 通过可能影响 Na 和 γ-氨基丁酸相关电流来增加动作电位的幅度和发射率。结果还证实了 TRPM5 通道在葡萄糖刺激条件下的显著作用。

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