Volatile general anaesthetics activate a novel neuronal K+ current
Volatile general anaesthetics activate a novel neuronal K+ current
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挥发性全身麻醉剂激活新型神经元 K 电流
作者：
N. Franks;W. R. Lieb
尽管全身麻醉的主要靶点是蛋白质1、2还是脂质3 -5仍有争议，但通常认为最终靶点是神经膜中的离子通道。找到这些靶点的一种方法是研究全身麻醉剂对已识别神经元的影响，其中对神经元活性的不同影响可以在分子水平上进行。在这里，我们报告说，在一组明显相同的软体动物神经元具有内源性放电活动，一个单一的细胞表现出不寻常的敏感性挥发性药物（在手术水平，完全抑制其活动）。我们进一步表明，这种敏感性是由于一种新的麻醉激活的K+电流，这是发现在敏感的细胞，但不是在周围的不敏感的细胞。这种K+电导不是明显的电压门控性的，只要麻醉剂存在就会持续存在。对麻醉剂的反应是完全可逆的，并且在低麻醉分压下饱和：氟烷的半最大反应发生在0.0063 atm，接近其在人体中的最小肺泡浓度（0.0075 atm）6。
Although it is still controversial whether the primary target sites underlying general anaesthesia are proteins1,2 or lipids3–5, it is generally thought that the ultimate targets are ion channels in nerve membranes. One approach to finding these targets is to study the effects of general anaesthetics on identified neurons, where differential effects on neuronal activity can be pursued to the molecular level. Here we report that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity). We further show that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. This K+ conductance is not appreciably voltage-gated and persists for as long as the anaesthetic is present. The response to anaesthetics is completely reversible and saturates at low anaesthetic partial pressures: the half-maximal response for halothane occurs at 0.0063 atm, close to its minimum alveolar concentration (0.0075 atm) in man6.