Kaminoh Y, Nishimura S, Kamaya H, Ueda I
Department of Anesthesia, University of Utah School of Medicine, Salt Lake City.
Biochim Biophys Acta. 1992 May 21;1106(2):335-43. doi: 10.1016/0005-2736(92)90014-d.
Nerve excitation generates heat and decreases the entropy (review by Ritchie and Keynes (1985) Q. Rev. Biophys. 18, 451-476). The data suggest the existence of at least two thermodynamically identifiable states: resting and excited, with a thermotropic transition between the two. We envision that nerve excitation is a transition between the two states of the excitation machinery consisting of proteins and lipids, rather than the sodium channel protein alone. Presumably, both proteins and lipids change their conformation at excitation. We proposed (Kaminoh et al. (1991) Ann. N.Y. Acad. Sci. 625, 315-317) that anesthesia occurs when compounds have a higher affinity to the resting state than to the excited state of excitable membranes, and that there is a critical temperature above which the affinity to the excited state becomes greater than to the resting state. When the temperature exceeds this critical level, compounds lose their anesthetic potency. We used thermotropic phase-transition of macromolecules as a model for the excitation process. Anesthetic alcohols decreased the main transition temperature of dipalmitoylphosphatidylcholine (DPPC) membranes and also the temperature of the alpha-helix to beta-sheet transition of poly(L-lysine). The affinity of alcohols to the high- and low-temperature states of the DPPC membranes were separately estimated. The difference in the affinity of n-alcohols to the liquid (high-temperature) and solid (low-temperature) states correlated with their anesthetic potency. It is not the total number of bound anesthetic molecules that determines the anesthesia, rather, the difference in the affinity between the higher and lower entropy states determines the effects. The critical temperatures of the long-chain alcohols were found to be lower than those of the short-chain alcohols. Cutoff occurs when the critical temperature of long-chain alcohols is below the physiological temperature, such that the anesthetic potency is not manifested in the experimental temperature range.
神经兴奋会产生热量并降低熵（见Ritchie和Keynes（1985年）《生物物理学季评》18卷，451 - 476页的综述）。数据表明至少存在两种可通过热力学识别的状态：静息态和兴奋态，两者之间存在热致转变。我们设想神经兴奋是由蛋白质和脂质组成的兴奋机制的两种状态之间的转变，而不仅仅是钠通道蛋白的转变。据推测，蛋白质和脂质在兴奋时都会改变其构象。我们曾提出（Kaminoh等人（1991年）《纽约科学院学报》625卷，315 - 317页），当化合物对可兴奋膜的静息态的亲和力高于对兴奋态的亲和力时会发生麻醉作用，并且存在一个临界温度，高于该温度时对兴奋态的亲和力会大于对静息态的亲和力。当温度超过这个临界水平时，化合物会失去其麻醉效力。我们将大分子的热致相变用作兴奋过程的模型。麻醉醇降低了二棕榈酰磷脂酰胆碱（DPPC）膜的主要转变温度，也降低了聚（L - 赖氨酸）从α - 螺旋向β - 折叠转变的温度。分别估算了醇类对DPPC膜高温态和低温态的亲和力。正醇类对液态（高温）和固态（低温）态的亲和力差异与其麻醉效力相关。决定麻醉作用的并非结合的麻醉分子总数，而是较高和较低熵态之间亲和力的差异决定了其效果。发现长链醇的临界温度低于短链醇的临界温度。当长链醇的临界温度低于生理温度时就会出现截止情况，以至于在实验温度范围内无法表现出麻醉效力。
