冷和薄荷醇受体TRPM8活性中相邻动力学状态停留时间的相关性分析
Analysis of correlations of dwell-times of adjacent kinetic states in the activity of the cold and menthol receptor TRPM8
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中文总结 AI 辅助
本研究针对TRPM8通道激活机制未充分探索的问题，提出一种分析相邻动力学状态停留时间相关性的单通道分析方法，可快速测试通道活性特性，通过比较分布差异开展研究。
中文摘要 AI 辅助
温度敏感性瞬时受体电位（TRP）通道在响应膜去极化和钙内流的细胞间信号传导中发挥重要作用。TRPM8离子通道作为主要的冷受体（神经传感器）已被研究，但其也可被电压、钙库耗竭以及薄荷醇、icilin等诱导冷感觉的脂质和其他配体激活。尽管近期在单通道水平研究这些通道取得进展，但其激活机制和时间过程仍未得到充分探索。我们提出一种用于单离子通道分析的方法，该方法阐明相邻开放状态与关闭状态停留时间之间相关性的存在。该方法的主要优势之一是其简洁性和快速数值实现，可作为通道活性特性的快速测试。我们的分析思路是研究给定轨迹（模拟或实验记录）导出的分布函数与无相关性的简单模型预测分布之间的差异，据此比较通道相邻开放和关闭状态持续时间之差的分布函数，以及类似的开放-关闭-开放-关闭状态序列的分布函数。
英文摘要
Temperature-sensitive transient receptor potential (TRP) channels play a significant role in intercellular signalling in response to membrane depolarisation and caclium influx. TRPM8 ion channels have been investigated as the main cold receptors (neurosensors), but they can also be activated by voltage, $Ca^{2+}$ store depletion, and certain lipids and other ligands that induce cold sensation (such as menthol and icilin). Despite recent progress in studying these channels at the single-channel level, the mechanisms and time course of their activation remain underexplored. We propose an approach to single-ion channel analysis that elucidates the presence of correlations between dwell-times of adjacent open and closed states. One of the major benefits of this approach is that it can serve as an express test of channel activity properties owing to its simplicity and fast numerical realization. The idea of our analysis is to study the difference between the distribution function derived from the given trace (simulated or experimentally recorded) and the predicted distributions of simple models without correlation. In this way, we compared the distribution function of the difference between the durations of the adjacent open and closed states of the channel, as well as that of a similar sequence of open-closed-open-closed states.
