Implications of a temperature-dependent heat capacity for temperature-gated ion channels.
Implications of a temperature-dependent heat capacity for temperature-gated ion channels.
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DOI：
10.1073/pnas.2301528120
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发表时间：
2023-06-13
影响因子：
11.1
通讯作者：
Aldrich, Richard W.
中科院分区：
文献类型：
--
作者：
Yeh, Frank;Jara-Oseguera, Andres;Aldrich, Richard W.
动物已经进化出高度敏感的温度门控离子通道，这种通道在加热或冷却时打开或关闭，将温度转换为电信号。以前关于温度门控机制的工作主要集中在作为构象变化驱动力的通道蛋白不同状态之间的热容差异。可溶性蛋白质可以表现出温度相关的热容差(ΔCP)。因此，我们扩展了温度门控理论以包括ΔCP的这种温度依赖关系，并发现这样的假设允许显著简化描述依赖于温度的通道激活的模型。温度影响所有分子过程的动力学和状态平衡分布，只有相对较窄的温度范围与生命相容-生物体必须避免可能导致物理损害或新陈代谢中断的极端温度。动物进化出一套感觉离子通道，其中许多属于瞬时受体电位阳离子通道家族，它们以惊人的灵敏度检测与生物相关的温度变化。根据特定的离子通道，加热或冷却引起通道的构象变化，使阳离子流入感觉神经元，产生电信号和感觉。导致这些离子通道温度敏感性升高的分子机制，以及使每个通道特别是热激活或冷激活的分子适应，在很大程度上是未知的。这些生物热敏传感器的两个构象之间的热容差(ΔCp)可以驱动它们的温度敏感性，但这些通道蛋白的ΔCp尚未得到实验测量。与通常认为ΔCP是恒定的假设相反，来自可溶性蛋白质的测量表明ΔCP很可能是温度的函数。通过研究线性温度依赖的ΔCP对离子通道开闭平衡的理论影响，我们揭示了一系列可能的通道行为，这些行为与通道活动的实验测量一致，并超出了通常认为可能的简单两态模型的范围，挑战了长期以来关于平衡时离子通道门控模型的假设。
Animals have evolved highly sensitive temperature-gated ion channels that open or close upon heating or cooling to transduce temperature into electrical signals. Previous work on the mechanism of temperature-gating has focused on differences in heat capacity between different states of a channel protein as a driving force for conformational change. Soluble proteins can exhibit temperature-dependent heat capacity differences (ΔCp). Therefore, we have extended the theory of temperature-gating to include such a temperature-dependence of ΔCp and find that such an assumption allows to significantly simplify models describing temperature-dependent channel activation. Temperature influences dynamics and state-equilibrium distributions in all molecular processes, and only a relatively narrow range of temperatures is compatible with life—organisms must avoid temperature extremes that can cause physical damage or metabolic disruption. Animals evolved a set of sensory ion channels, many of them in the family of transient receptor potential cation channels that detect biologically relevant changes in temperature with remarkable sensitivity. Depending on the specific ion channel, heating or cooling elicits conformational changes in the channel to enable the flow of cations into sensory neurons, giving rise to electrical signaling and sensory perception. The molecular mechanisms responsible for the heightened temperature-sensitivity in these ion channels, as well as the molecular adaptations that make each channel specifically heat- or cold-activated, are largely unknown. It has been hypothesized that a heat capacity difference (ΔCp) between two conformational states of these biological thermosensors can drive their temperature-sensitivity, but no experimental measurements of ΔCp have been achieved for these channel proteins. Contrary to the general assumption that the ΔCp is constant, measurements from soluble proteins indicate that the ΔCp is likely to be a function of temperature. By investigating the theoretical consequences for a linearly temperature-dependent ΔCp on the open–closed equilibrium of an ion channel, we uncover a range of possible channel behaviors that are consistent with experimental measurements of channel activity and that extend beyond what had been generally assumed to be possible for a simple two-state model, challenging long-held assumptions about ion channel gating models at equilibrium.
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DOI：
10.1073/pnas.0406773101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Brauchi, S;Orio, P;Latorre, R
通讯作者：
Latorre, R
DOI：
10.1002/prot.340220410
发表时间：
1995-08-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
GOMEZ, J;HILSER, VJ;FREIRE, E
通讯作者：
FREIRE, E
影响因子：
2.9
作者：
HYRE, DE;SPICER, LD
通讯作者：
SPICER, LD
影响因子：
3.4
作者：
Liu, Beiying;Qin, Feng
通讯作者：
Qin, Feng
影响因子：
4
作者：
Latorre, Ramon;Brauchi, Sebastian;Vargas, Guillermo
通讯作者：
Vargas, Guillermo