T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray
- T-type channels control the opioidergic descending analgesia at the low threshold-spiking GABAergic neurons in the periaqueductal gray
- Cheongdahm Park; 김종현; 윤보은; Choi Eui Ju; 이창준; 신희섭
- opioid-descending analgesia; α1G; morphine; stress; calcium-activated potassium channel; afterhyperpolarization
- Issue Date
- Proceedings of the National Academy of Sciences of the United States of America
- VOL 107, NO 33, 14857-14862
- 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.
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