Pocock G, Richards C D
Department of Physiology, Royal Free Hospital School of Medicine, London.
Br J Anaesth. 1993 Jul;71(1):134-47. doi: 10.1093/bja/71.1.134.
To understand the cellular and molecular basis of the anaesthetic state, it is important to remember that, in the intact CNS, synapses operate within elaborate nerve networks. From the data presented above, it is evident that block of impulse conduction in presynaptic fibres does not explain the effects of most anesthetics on synaptic activity. This is not surprising since some anaesthetics, the barbiturates in particular, may both depress excitation and enhance inhibition. General anaesthetics modulate the activity of presynaptic voltage-gated calcium channels and this appears to be sufficient to account for the reduction in transmitter secretion they produce. Transmitter operated ion channels in the postsynaptic membrane are modulated by smaller concentrations of anaesthetics than are required to modulate the presynaptic voltage-gated calcium channels. For this reason, transmitter operated channels appear to represent a major target site for anaesthetics. Finally, there are subtle effects of anaesthetics on the patterns of impulse propagation in nerve axons and on action potential generation in the cell body which result from modulation of membrane excitability. The overall effect of an anaesthetic agent depends on summation of events occurring at the many individual synapses and neurones that make up the network. The effects of anaesthetics on different neuronal pathways may therefore depend on the nature of the receptors and ion channels of the cells that comprise the network. The anaesthetic state may be the result of all these actions, but the characteristics of the state may differ somewhat from agent to agent.
为了理解麻醉状态的细胞和分子基础，重要的是要记住，在完整的中枢神经系统中，突触在复杂的神经网络中发挥作用。从上述数据可以明显看出，突触前纤维中冲动传导的阻断并不能解释大多数麻醉药对突触活动的影响。这并不奇怪，因为一些麻醉药，尤其是巴比妥类药物，可能既抑制兴奋又增强抑制。全身麻醉药可调节突触前电压门控钙通道的活性，这似乎足以解释它们所导致的递质分泌减少。与调节突触前电压门控钙通道所需的麻醉药浓度相比，突触后膜中的递质门控离子通道可被更低浓度的麻醉药所调节。因此，递质门控通道似乎是麻醉药的主要作用靶点。最后，麻醉药对神经轴突中冲动传播模式以及细胞体中动作电位产生有微妙的影响，这些影响是由膜兴奋性的调节所致。麻醉剂的总体作用取决于在构成网络的许多单个突触和神经元处发生的事件的总和。因此，麻醉药对不同神经元通路的影响可能取决于构成该网络的细胞的受体和离子通道的性质。麻醉状态可能是所有这些作用的结果，但不同药物导致的麻醉状态特征可能会有所不同。
