T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray

Title
T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray
Authors
Cheongdahm Park김종현윤보은Choi Eui Ju이창준신희섭
Keywords
opioid-descending analgesia; α1G; morphine; stress; calcium-activated potassium channel; afterhyperpolarization
Issue Date
2010-08
Publisher
Proceedings of the National Academy of Sciences of the United States of America
Citation
VOL 107, NO 33, 14857-14862
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.
URI
http://pubs.kist.re.kr/handle/201004/38228
ISSN
0027-8424
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KIST Publication > Article
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