Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices.
Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices.
复制标题
DOI：
10.1186/1471-2202-5-52
复制
发表时间：
2004-12-03
期刊：
影响因子：
2.4
通讯作者：
MacIver MB
中科院分区：
文献类型：
--
作者：
Pittson S;Himmel AM;MacIver MB
麻醉是由中枢神经系统功能抑制引起的，然而，这种抑制作用的部位和作用机制仍然不明确。本研究比较并对比了五种全身麻醉剂对海马切片 CA1 区域突触回路的影响。在临床相关且等效的浓度下，谷氨酸介导的兴奋性突触和 GABA 介导的抑制性突触具有明显的突触前和突触后麻醉作用。此外，还观察到 CA1 神经元响应直流电去极化放电对膜兴奋性的抑制作用。其中几个部位的联合作用导致 CA1 回路抑制，但对于所研究的每种麻醉剂，每个部位的相对影响程度不同。例如，大部分丙泊酚的抑制作用（> 70 %）可以用 GABA 拮抗剂逆转，但异氟烷的抑制作用只有一小部分被逆转（< 20 %）。谷氨酸突触的差异也很明显——戊巴比妥抑制传输> 50%，但硫喷妥钠仅抑制< 25%。这些结果尽管可能与麻醉相关，但表明全身麻醉药作用于几个离散的部位，支持麻醉作用的多部位、药剂特定理论。没有任何单一效应位点（例如 GABA 突触）或作用机制（例如膜兴奋性降低）可以解释所研究的任何麻醉剂产生的所有效应。
Anesthesia is produced by a depression of central nervous system function, however, the sites and mechanisms of action underlying this depression remain poorly defined. The present study compared and contrasted effects produced by five general anesthetics on synaptic circuitry in the CA1 region of hippocampal slices. At clinically relevant and equi-effective concentrations, presynaptic and postsynaptic anesthetic actions were evident at glutamate-mediated excitatory synapses and at GABA-mediated inhibitory synapses. In addition, depressant effects on membrane excitability were observed for CA1 neuron discharge in response to direct current depolarization. Combined actions at several of these sites contributed to CA1 circuit depression, but the relative degree of effect at each site was different for each anesthetic studied. For example, most of propofol's depressant effect (> 70 %) was reversed with a GABA antagonist, but only a minor portion of isoflurane's depression was reversed (< 20 %). Differences were also apparent on glutamate synapses-pentobarbital depressed transmission by > 50 %, but thiopental by only < 25 %. These results, in as much as they may be relevant to anesthesia, indicate that general anesthetics act at several discrete sites, supporting a multi-site, agent specific theory for anesthetic actions. No single effect site (e.g. GABA synapses) or mechanism of action (e.g. depressed membrane excitability) could account for all of the effects produced for any anesthetic studied.
登录
查看更多内容
影响因子：
5.3
作者：
Bai, DL;Pennefather, PS;Orser, BA
通讯作者：
Orser, BA
影响因子：
6.1
作者：
Albertson, TE;Walby, WF;Joy, RM
通讯作者：
Joy, RM
影响因子：
9.8
作者：
Gredell, JA;Turnquist, PA;Pearce, RA
通讯作者：
Pearce, RA
影响因子：
7.3
作者：
Kirson, ED;Yaari, Y;Perouansky, M
通讯作者：
Perouansky, M
DOI：
10.1016/0013-4694(81)90142-5
发表时间：
1981-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
LEUNG, LWS
通讯作者：
LEUNG, LWS