Abstract:
Transient receptor potential (TRP) ion channels are among the most well-studied classes of temperature-sensing molecules. Yet, the molecular mechanism and thermodynamic basis for the temperature sensitivity of TRP channels remains to this day poorly understood. One hypothesis is that the temperature-sensing mechanism can simply be described by a difference in heat capacity between the closed and open channel states. While such a two-state model may be simplistic it nonetheless has descriptive value, in the sense that it can be used to compare overall temperature sensitivity between different channels and mutants. Here, we introduce a mathematical framework based on the two-state model to reliably extract temperature-dependent thermodynamic potentials and heat capacities from measurements of equilibrium constants at different temperatures. Our framework is implemented in an open-source data analysis package that provides a straightforward way to fit both linear and nonlinear van \'t Hoff plots, thus avoiding some of the previous, potentially erroneous, assumptions when extracting thermodynamic variables from TRP channel electrophysiology data.
摘要:
瞬时受体电位(TRP)离子通道是研究最充分的温度传感分子类别之一。然而,TRP通道温度敏感性的分子机制和热力学基础至今仍知之甚少。一个假设是温度感测机制可以简单地通过闭合和开放通道状态之间的热容量差异来描述。虽然这样的两状态模型可能很简单,但它具有描述价值,从某种意义上说,它可以用来比较不同通道和突变体之间的整体温度敏感性。这里,我们引入了基于两状态模型的数学框架,以从不同温度下的平衡常数测量中可靠地提取与温度相关的热力电势和热容。我们的框架是在一个开源数据分析包中实现的,它提供了一种简单的方法来拟合线性和非线性范特霍夫图,从而避免了以前的一些,潜在的错误,从TRP通道电生理数据中提取热力学变量时的假设。