The blockade of NMDA receptor ion channels by ketamine is enhanced in developing rat cortical neurons.
The blockade of NMDA receptor ion channels by ketamine is enhanced in developing rat cortical neurons.
复制标题
氯胺酮对 NMDA 受体离子通道的阻断在发育中的大鼠皮质神经元中得到增强
DOI：
10.1016/j.neulet.2013.01.034
复制
发表时间：
2013-02-28
影响因子：
2.5
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Jin J;Gong K;Zou X;Wang R;Lin Q;Chen J
氯胺酮是一种NMDAR的非竞争性拮抗剂，在许多儿科手术中常用作解离麻醉剂。氯胺酮主要通过阻断NMDA配体门控通道起作用。实验研究表明，用于诱导临床相关麻醉的氯胺酮可选择性地对未成熟的脑神经元产生神经毒性效应，如细胞凋亡。然而，潜在的机制仍不清楚。本研究采用全细胞膜片钳记录技术，在体外制备前脑片，从药理学角度分析了氯胺酮对未成熟神经元和成熟神经元NMDAR通道活动的影响差异。以诱发的NMDAR介导的兴奋性突触后电流(EEPSCs)的形式记录新生和成年大鼠前脑的NMDAR通道活动。结果表明，氯胺酮对未成熟神经元和成熟神经元的eEPSCs均有抑制作用，且呈剂量依赖性。然而，在脑片上应用不同浓度的氯胺酮时，新生神经元比成年神经元受到更广泛的抑制。检测氯胺酮洗脱后1、3、6h对eEPSCs的阻断作用。未成熟神经元的eEPSCs在清洗后6h仍有明显抑制。相反，成熟神经元对eEPSCs的阻断完全从氯胺酮的抑制中恢复，且呈时间依赖关系。这些结果表明，氯胺酮对未成熟神经元NMDAR通道的阻断作用大于成熟神经元，且持续时间更长。这种不同的效应很可能是导致发育中大脑神经元更容易受到氯胺酮诱导的神经毒性的关键环节。
Ketamine is a non-competitive antagonist of NMDA receptors (NMDARs) commonly used as a dissociative anesthetic in many pediatric procedures. Ketamine acts primarily by blocking NMDA ligand-gated channels. Experimental studies indicate that ketamine administration used for inducing clinically relevant anesthesia can lead to neurotoxic effects, such as apoptosis, selectively on immature brain neurons. However, the underlying mechanisms remain unclear. This study used whole-cell patch-clamp recordings in an in vitro preparation of forebrain slices to analyze pharmacologically the differences in the effects of ketamine administration on the NMDAR channel activity between immature and mature neurons. NMDAR channel activity was recorded in the form of evoked NMDAR-mediated excitatory postsynaptic currents (eEPSCs) from the forebrain of both neonatal and adult rats. Results show that ketamine inhibited eEPSCs in a dose-dependent manner in both immature and mature neurons. However, at each concentration of ketamine applied to the brain slice, a more extensive inhibition could be seen in neonatal neurons than in adult neurons. Further, the blocking effect of ketamine on eEPSCs was measured during the period of 1, 3, and 6 h after ketamine washout. Inhibition of eEPSCs in immature neurons was still evident 6 h after washout. In contrast, the blockade of eEPSCs in mature neurons recovered completely from the inhibition by ketamine in a time-dependent manner. These results indicate that ketamine produces a greater and longer blocking effect on NMDAR channels in immature neurons than in mature neurons. This differential effect is likely to be a critical link to the higher vulnerability to ketamine-induced neurotoxicity in neurons of the developing brain.
登录
查看更多内容
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.1523/jneurosci.4022-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Foster KA;McLaughlin N;Edbauer D;Phillips M;Bolton A;Constantine-Paton M;Sheng M
通讯作者：
Sheng M
影响因子：
3.8
作者：
Scallet, AC;Schmued, LC;Hanig, JP
通讯作者：
Hanig, JP
影响因子：
5.3
作者：
Sobczyk, A;Scheuss, V;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
2
作者：
Jeun, Seung Hyun;Cho, Hyeong Seok;Sung, Ki-Wug
通讯作者：
Sung, Ki-Wug