A hypothesis on the origin and evolution of the response to inhaled anesthetics.
A hypothesis on the origin and evolution of the response to inhaled anesthetics.
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DOI：
10.1213/ane.0b013e31817ee684
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发表时间：
2008-09
影响因子：
5.7
通讯作者：
Sonner, James M.
中科院分区：
文献类型：
--
作者：
Sonner, James M.
提出了一种进化论来解释为什么生物体对吸入麻醉剂有反应。据推测，今天的生物体对吸入麻醉剂有反应，因为它们的离子通道对吸入麻醉剂敏感，这是由于单细胞生物体中对麻醉剂敏感的祖先离子通道的共同血统（即，对麻醉剂的反应不是作为神经系统的适应而产生的，而是作为多细胞起源之前的离子通道的适应而产生的）。这种敏感性可能通过多细胞生物体突触的持续选择而得到改善。特别是，假设单细胞生物体中选择的有益特征是离子通道对环境中存在的化合物的协调反应，这些化合物影响离子通道的构象平衡，这种协调反应防止了正电荷进入细胞的有害后果，从而增加了生物体的适应性，这些化合物（可能包括有机阴离子、阳离子和两性离子以及不带电的化合物）模仿吸入麻醉剂，因为它们是通过改变与通道功能耦合的双层特性来实现界面活性和调制离子通道功能。所提出的假设与吸入麻醉剂的已知特性一致。此外，它还可以对非挥发性化合物进行可测试的实验预测，这些化合物对离子通道和动物具有类似麻醉剂的调节作用，包括可能调节健康和疾病中离子通道功能的内源性化合物。后者包括在某些类型的终末期器官衰竭和遗传代谢疾病中升高的代谢物。其中一些预测已经过测试并被证明是正确的。提出了吸入麻醉药反应的起源和演变的假设，并对该理论进行了实验预测。
An evolutionary narrative explaining why organisms respond to inhaled anesthetics is proposed. It is conjectured that organisms today respond to inhaled anesthetics because their ion channels are sensitive to inhaled anesthetics by virtue of common descent from ancestral, anesthetic-sensitive ion channels in one-celled organisms (i.e., that the response to anesthetics did not arise as an adaptation of the nervous system, but rather of ion channels that preceded the origin of multicellularity). This sensitivity may have been refined by ongoing selection at synapses in multicellular organisms. In particular, it is hypothesized that the beneficial trait that was selected for in one-celled organisms was the coordinated response of ion channels to compounds that were present in the environment which influenced the conformational equilibrium of ion channels that this coordinated response prevented the deleterious consequences of entry of positive charges into the cell, thereby increasing the fitness of the organism that these compounds (which may have included organic anions, cations, and zwitterions as well as uncharged compounds) mimicked inhaled anesthetics in that they were interfacially active, and modulated ion channel function by altering bilayer properties coupled to channel function. The proposed hypothesis is consistent with known properties of inhaled anesthetics. In addition, it leads to testable experimental predictions of nonvolatile compounds having anesthetic-like modulatory effects on ion channels and in animals, including that of endogenous compounds that may modulate ion channel function in health and disease. The latter included metabolites which are elevated in some types of end stage organ failure, and genetic metabolic diseases. Several of these predictions have been tested and proved to be correct. A hypothesis for the origin and evolution of the response to inhaled anesthetics is offered, and experimental predictions of this theory are made.
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