文章基本信息

标题：T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray
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作者：Cheongdahm Park ; Jong-Hyun Kim ; Bo-Eun Yoon 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：33
页码：14857-14862
DOI：10.1073/pnas.1009532107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Endogenous opioids generate analgesic signals in the periaqueductal gray (PAG). However, because cell types in the PAG are difficult to identify, its neuronal mechanism has remained poorly understood. To address this issue, we characterized PAG neurons by their electrical properties using differentially labeled GABAergic and output neurons in the PAG. We found that GABAergic neurons were mostly fast-spiking cells and could be further divided into two distinct classes: with or without low-threshold spikes (LTS) driven by T-type channels. In contrast, the PAG output neurons lacked LTS and showed heterogeneous firing patterns. To reveal the function of the LTS, we examined the mutant mice lacking the {alpha}1G T-type channels ({alpha}1G-/-). The mutant mice lacked LTS in the fast-spiking GABAergic neurons of the PAG and unexpectedly showed impaired opioid-dependent analgesia; a similar phenotype was reproduced in PAG-specific {alpha}1G-knockdown mice. Electrophysiological analyses revealed functional expression of {micro}-opioid receptors in the low threshold-spiking GABAergic neurons. These neurons in the mutant lacking LTS showed markedly enhanced discharge activities, which led to an augmented inhibition of output neurons. Furthermore, the impaired analgesia observed in {alpha}1G-/- mice was reversed by blocking local GABAA receptors. These results indicate that {alpha}1G T-type channels are critical for the opioidergic descending analgesia system in the PAG.
关键词：opioid-descending analgesia ; α1G ; morphine ; stress ; calcium-activated potassium channel ; afterhyperpolarization