Steinbach J H, Sine S M
Soc Gen Physiol Ser. 1987;41:19-42.
In summary, the AChRs on BC3H-1 cells behave in a fashion consistent with the major properties expected of muscle nicotinic AChRs. The results we have discussed here provide a quantitative description of some of the steps in receptor activation, and give a general picture of the functional states the AChR adopts. The results provide a framework for biochemical and ultrastructural studies of the AChR as well. One clear problem is that the receptor with an open channel is a very low probability state at equilibrium, at any concentration. A second problem is the postulated existence of closed channel states associated with brief-duration openings. It is not known what the probability is that a receptor is in such a state, so even "resting" receptors at low agonist concentrations may be in several functional states. At high agonist concentrations the receptor population goes through several transient states before reaching the final equilibrium state. At 11 degrees C, with a high concentration of ACh (greater than 0.3 mM) receptors with open channels appear rapidly (rate approximately 500 sec-1). Initially, there is a high probability that a receptor is both doubly liganded and has an open channel (0.9, Fig. 6). However, the predesensitized state develops rapidly (approximately 30 sec-1), and eventually the probability reaches about 0.4 that doubly liganded receptors are predesensitized. The short-lived desensitized state develops at a rate of about 3 sec-1. After a second or so, the distribution is about 0.3:0.2:0.5 for AChRs between receptors with open channels, predesensitized receptors, and short-lived desensitized receptors. Long-lived desensitization develops at a rate of about 0.5 sec-1, but at equilibrium the probability that a receptor is in this state is above 0.99. For AChRs on BC3H-1 cells, and most likely all AChRs, biochemical and structural studies need to be made in a narrow time window to catch an appreciable fraction of the receptors in any of the transient functional states described. Only time-resolved biochemical studies will provide the structural information necessary to work out the relationship between structure and function for the ACh receptor and give some substance to the ghostly kinetic states necessary to describe channel function.
总之，BC3H - 1细胞上的乙酰胆碱受体（AChRs）的行为方式与肌肉烟碱型乙酰胆碱受体预期的主要特性一致。我们在此讨论的结果对受体激活过程中的一些步骤进行了定量描述，并给出了AChR所采用的功能状态的总体情况。这些结果也为AChR的生化和超微结构研究提供了一个框架。一个明显的问题是，在任何浓度下，处于通道开放状态的受体在平衡时都是一种概率极低的状态。第二个问题是假定存在与短暂开放相关的通道关闭状态。目前尚不清楚受体处于这种状态的概率是多少，所以即使在低激动剂浓度下的“静息”受体也可能处于几种功能状态。在高激动剂浓度下，受体群体在达到最终平衡状态之前会经历几个瞬态。在11摄氏度时，使用高浓度的乙酰胆碱（大于0.3 mM），通道开放的受体迅速出现（速率约为500秒-1）。最初，受体同时被双重配体结合且通道开放的概率很高（0.9，图6）。然而，预脱敏状态迅速发展（约30秒-1），最终双重配体结合的受体处于预脱敏状态的概率达到约0.4。短暂的脱敏状态以约3秒-1的速率发展。大约一秒钟后，通道开放的受体、预脱敏受体和短暂脱敏受体之间的AChR分布约为0.3:0.2:0.5。长期脱敏以约0.5秒-1的速率发展，但在平衡时受体处于这种状态的概率高于0.99。对于BC3H - 1细胞上的AChR，很可能所有的AChR都是如此，需要在一个狭窄的时间窗口内进行生化和结构研究，以便捕捉到处于任何所述瞬态功能状态的可观比例的受体。只有时间分辨生化研究才能提供必要的结构信息，以阐明ACh受体的结构与功能之间的关系，并为描述通道功能所需的幽灵般的动力学状态提供一些实质内容。
