Gomez Renato S, Guatimosim Cristina
Departamento de Cirurgia, Faculdade de Medicina da UFMG, Belo Horizonte-Minas Gerais, Brazil.
Curr Drug Targets CNS Neurol Disord. 2003 Apr;2(2):123-9. doi: 10.2174/1568007033482940.
There have been extensive efforts to characterize the mechanism of action of volatile anesthetics, but their molecular and cellular actions are still a matter of debate. Volatile anesthetics act primarily on synaptic transmission in the central nervous system but proof of this as the predominant mechanism of action remains elusive. Changes in neurotransmitter release may relate to direct interaction of the anesthetic molecule with an ion channel protein or synaptic protein, but can also be a consequence of alterations in intracellular signaling. Calcium is one of the most important messengers in cells and its intracellular concentration may be modified by several agents including volatile anesthetics. Neuronal excitability is in part determined by calcium availability that is controlled by several mechanisms. Because voltage-gated calcium channels (VGCC) play a key role in controlling Ca2+ entry and in initiating cellular responses to stimulation through an elevation of intracellular calcium concentration (Ca2+), they are thought to be one of the targets for volatile anesthetics. However, Ca2+ can also be altered without the participation of VGCC through receptor-mediated pathways. Indeed, calcium homeostasis is also controlled by plasma membrane Ca2+ -adenosine triphosphatase, sarcoplasmic-endoplasmic reticular Ca2+ -ATPase, the Na+ -Ca2+ exchanger, and mitochondrial Ca2+ sequestration. Alteration of any of those mechanisms that control Ca2+ may lead to a change in presynaptic transmission or postsynaptic excitability. Here we will review some of the recent progress in identifying putative actions of volatile anesthetics, specifically the effect on intracellular calcium homeostasis in neurons.
人们已经进行了广泛的努力来描述挥发性麻醉剂的作用机制，但其分子和细胞作用仍存在争议。挥发性麻醉剂主要作用于中枢神经系统的突触传递，但作为主要作用机制的证据仍然难以捉摸。神经递质释放的变化可能与麻醉剂分子与离子通道蛋白或突触蛋白的直接相互作用有关，但也可能是细胞内信号改变的结果。钙是细胞中最重要的信使之一，其细胞内浓度可能会受到包括挥发性麻醉剂在内的多种因素的影响。神经元兴奋性部分取决于由多种机制控制的钙可用性。由于电压门控钙通道（VGCC）在控制Ca2+内流以及通过提高细胞内钙浓度（[Ca2+]i）引发细胞对刺激的反应中起关键作用，因此它们被认为是挥发性麻醉剂的靶点之一。然而，[Ca2+]i也可以在没有VGCC参与的情况下通过受体介导的途径发生改变。实际上，钙稳态还受质膜Ca2+-三磷酸腺苷酶、肌浆网-内质网Ca2+-ATP酶、Na+-Ca2+交换体和线粒体钙螯合的控制。控制[Ca2+]i的任何一种机制的改变都可能导致突触前传递或突触后兴奋性的变化。在这里，我们将回顾在确定挥发性麻醉剂的假定作用，特别是对神经元细胞内钙稳态的影响方面的一些最新进展。
