Yost C S
Department of Anesthesia, University of California, San Francisco 94143, USA.
Curr Drug Targets. 2000 Sep;1(2):207-17. doi: 10.2174/1389450003349335.
Despite over 150 years of clinical use, the mechanism and molecular elements by which volatile anesthetics produce unconsciousness are not established. Although enhanced activity of inhibitory neurotransmitter systems (GABAA) and depression of excitatory neurotransmitter systems (NMDA) probably contribute to the anesthetic state, the role of other ion channels families have also been studied. Potassium channels represent the largest group of mammalian ion channels and their activity to reduce neuronal excitability makes them viable candidates as sites of anesthetic action. Several studies from the 1970's and 80's identified volatile anesthetic enhancement of neuronal potassium currents. More recently, a new family of K channels with a unique structure (tandem pore domains) that may be responsible for baseline or background K currents have been isolated and some members of this family can be activated by volatile anesthetics. These emerging findings suggest a new molecular mechanism by which volatile anesthetics may mediate central nervous system depression.
尽管挥发性麻醉剂已有150多年的临床应用历史，但其产生意识丧失的机制和分子因素尚未明确。虽然抑制性神经递质系统（GABAA）活性增强和兴奋性神经递质系统（NMDA）受抑制可能促成麻醉状态，但其他离子通道家族的作用也已得到研究。钾通道是哺乳动物离子通道中最大的一类，其降低神经元兴奋性的活性使其成为麻醉作用位点的潜在候选者。20世纪70年代和80年代的多项研究证实了挥发性麻醉剂可增强神经元钾电流。最近，一种具有独特结构（串联孔结构域）的新型钾通道家族被分离出来，该家族可能负责基线或背景钾电流，并且该家族的一些成员可被挥发性麻醉剂激活。这些新发现提示了一种挥发性麻醉剂可能介导中枢神经系统抑制的新分子机制。
