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

Cheongdahm Park, Jong Hyun Kim, Bo Eun Yoon, Eui Ju Choi, C. Justin Lee, Hee Sup Shin

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14857-14862
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number33
DOIs
Publication statusPublished - 2010 Aug 17

Keywords

  • Afterhyperpolarization
  • Calcium-activated potassium channel
  • Morphine
  • Opioid-descending analgesia
  • Stress
  • α1G

ASJC Scopus subject areas

  • General

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