한빛사논문
- 조회5,798
Abstract
Cheongdahm Parka , b , Jong-Hyun Kim a , b , Bo-Eun Yoon a , c , Eui-Ju Choi b , C. Justin Lee a , c , and Hee-Sup Shin a , 1
aCenter for Neural Science, Future Fusion Technology Laboratory, Korea Institute of Science and Technology, Seoul 136-791, Korea;
bNational Creative Research Initiative Center for Cell Death, Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea; and
cNeuroscience Program, University of Science and Technology, Daejeon 305-701, Korea
Contributed by Hee-Sup Shin, July 12, 2010 (sent for review June 3, 2010)
Abstract
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 α1G T-type channels (α1G-/-). 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 α1G-knockdown mice. Electrophysiological analyses revealed functional expression of μ-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 α1G-/- mice was reversed by blocking local GABAA receptors. These results indicate that α1G T-type channels are critical for the opioidergic descending analgesia system in the PAG.
opioid-descending analgesia, α1G, morphine, stress, calcium-activated potassium channel, afterhyperpolarization
Footnotes
1To whom correspondence should be addressed.
Author contributions: C.P., C.J.L., and H.-S.S. designed research; C.P., J.-H.K., and B.-E.Y. performed research; C.P., J.-H.K., and B.-E.Y. analyzed data; and C.P., E.-J.C., C.J.L., and H.-S.S. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1009532107/-/DCSupplemental.
논문정보
- Research article
- 2010년 08월 (BRIC 등록일 )
- 국내 연구진
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